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Brachytherapy Strand Localization Using Average-Reflected-Power Ultrasound Data and Echogenic Echo Strands Zheng, Jack 2010

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Brachytherapy Strand LocalizationUsing Average-Re ected-PowerUltrasound Data and EchogenicEchoStrandTMbyJack ZhengA THESIS SUBMITTED IN PARTIAL FULFILLMENT OFTHE REQUIREMENTS FOR THE DEGREE OFBACHELOR OF SCIENCEinThe Faculty of Science(Honors Biophysics)THE UNIVERSITY OF BRITISH COLUMBIA(Vancouver)August 2010c Jack Zheng 2010AbstractThis project aims to determine if average-re ected-power ultrasound imaging and echogenicEchoStrandTM is able to improve real-time brachytherapy strand localization on the ultrasound.The  rst part of the experiment compares both regular and EchoStrandTM image intensities atvarious orientations and the ability to attribute these strands to di erent image planes. The sec-ond part directly compares the abilities of average-re ected-image imaging and regular B-Modeimaging in contrasting both strand types against a noisy background.The EchoStrandTM is visually and quantitatively found to give a stronger intensity responseand better contrast to background noise ratio than regular strands particularly at non-parallelstrand orientations. Both strands can be attributed to associated image plane with a small degreeof error, though this was more di cult for regular strands at non-parallel orientations. Theaverage-re ected-power imaging technique greatly enhances the contrast to background of bothstrands across all orientations compared with regular B-Mode imaging. Overall, the combinationof EchoStrandTM and average-re ected-power imaging is found to improve the strand localizationabilities of the ultrasound. A clinical study can be conducted to further build on the conclusionsarrived in this project.Jack Zheng - jackz@interchange.ubc.caiiTable of ContentsAbstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iiTable of Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iiiList of Figures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vAcknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viiDedication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viii1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Brachytherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32.2 Brachytherapy Planning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.3 Seed Placement and Dosimetry Considerations . . . . . . . . . . . . . . . . . . . . 72.4 The Implantation Procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82.5 Intraoperative Modi cation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92.6 Regular and EchoStrandsTM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Ultrasound Image Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143.1 Basics of Ultrasound Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143.2 Image-Based Strand Localization Considerations . . . . . . . . . . . . . . . . . . . 163.2.1 Localizing to Image Planes . . . . . . . . . . . . . . . . . . . . . . . . . . . 163.2.2 E ects of Strand Orientation on Ultrasound Re ectance . . . . . . . . . . 173.3 Average-Re ected-Power Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 Quantitative Strand Intensity Response Measurements . . . . . . . . . . . . . . 234.1 Experiment Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234.2 Image Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28iiiTable of Contents5 Contrast to Noise Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355.1 Experiment Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355.2 Image Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386 Discussions, Conclusions and Future Work . . . . . . . . . . . . . . . . . . . . . . 426.1 Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 426.2 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 456.3 Future Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47ivList of Figures2.1 During volume study, the TRUS probe collects a set of consecutive transverseimages encompassing the prostate from its apex to base. . . . . . . . . . . . . . . . 42.2 A sample planning report showing needle and seed information. . . . . . . . . . . . 62.3 3D Reconstruction of a set of implanted brachytherapy seeds determined using uoroscopy superimposed over a reconstruction of the respective planned positions. 92.4 Ultrasound B-Mode Images of a brachytherapy seed n tissue . . . . . . . . . . . . . 112.5 Illustration of the di erence between an EchoStrandTM and a regular strand. . . . 123.1 Ultrasound data re ects the presence of re ective boundaries in the path of theultrasound beam. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143.2 Transverse images are formed by sets of beams generated by a radial crystal arraywhile sagittal images are formed by a crystal array running along the length of theTRUS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153.3 Strand positioning in three dimensional space can be determined by a sagittalimage sweep using the TRUS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173.4 Ultrasound echoes are re ected uniformly in cases of specular re ection and arescattered in non-specular re ection. . . . . . . . . . . . . . . . . . . . . . . . . . . . 183.5 Average-re ected-power intensity responses of seeds at di erent orientations. . . . 193.6 Illustration of the average-re ected-power calculation process. . . . . . . . . . . . . 204.1 The Ultrasonix 500 RP PC-based Ultrasound System. . . . . . . . . . . . . . . . . 244.2 The strand rotational setup. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254.3 The TRUS probe, encoder and support structure. . . . . . . . . . . . . . . . . . . . 264.4 Rotation of the TRUS around its axis serves to sweep its sagittal image plane overthe imaged strand. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274.5 The intensity response of a strand in an ultrasound image is sampled by creatingten ROI along the length of the strand. . . . . . . . . . . . . . . . . . . . . . . . . 284.6 Beam sweep plots for strand of orientations from 0 to 10 degrees in average-re ected-power images. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304.7 Beam sweep plots for strand of orientations from 12 to 22 degrees. . . . . . . . . . 314.8 B-Mode images of strands at di erent orientations. . . . . . . . . . . . . . . . . . . 32vList of Figures4.9 Average-re ected-power images of strands at di erent orientations. . . . . . . . . . 334.10 Plot of average-re ected-power intensity responses of strand at di erent orientations. 345.1 Composition of the cellulose phantom used in this experiment. . . . . . . . . . . . 355.2 The experiment setup for the contrast to noise analysis. . . . . . . . . . . . . . . . 375.3 B-Mode images of strands in phantom at di erent orientations. . . . . . . . . . . . 395.4 Average-re ected-power images of strands at di erent orientations. . . . . . . . . . 405.5 Log of contrast-to-noise ratio plotted against the strand orientation for di erentimaging methods and regular strands and EchoStrandTM. . . . . . . . . . . . . . . 41viAcknowledgementsI would like to thank my supervisor Dr. Tim Salcudean along with Dr. Mehdi Moradi (Post-doctoral Fellow) from the UBC Electrical and Computer Engineering Department for theirtremendous guidance and support. Special thanks to Xu Wen for his work in developing theaverage-re ected-power imaging method as well as other members of the UBC Robotics andControl Laboratory for their contribution to the success of this project.viiDedicationTo my parents for instilling in me the drive to continually learn and grow. Thank you.viiiChapter 1IntroductionProstate cancer is the most commonly diagnosed form of cancer in Canadian men and is the thirdleading cause of male cancer deaths. It is estimated that 25,500 new cases of prostate cancer willbe diagnosed in 2009 alone and 4,400 Canadian men will die from it[6].Brachytherapy has increasingly gained acceptance as a minimally invasive procedure thatdelivers successful treatment outcomes against prostate cancer[10]. In brachytherapy, rows ofradioactive metal seeds are sutured together into long strands which are then implanted into apatient’s prostate. The radioactive seeds within each strand locally irradiate and kill surround-ing cancerous tissues. The implantation process is guided by a transrectal ultrasound probe(TRUS)[11].The two goals in brachytherapy are to deliver an adequate dose of radiation to cancer-ous tissues of the prostate while minimizing radiation to the surrounding organs of the ure-thra and rectum. Successfully achieving these reduces both post-operation recurrence rates andcomplications[11]. Radioactive seed positions are implanted in a pattern that best meet thesegoals.However, insertion errors can lead to large deviations between where the seeds are actuallyplaced and where they should be placed. These errors create a drastically di erent dosimetrypro le and negatively impact the outcome of the procedure. Being able to modify the plan duringthe procedure is required to minimize the e ects of these errors[7, 13]. To perform these modi -cations accurately, an up-to-date dosimetry pro le must be calculated based on the positions ofthe already implanted seeds. This type of calculation is called real-time dosimetry[11].Accurate real-time dosimetry depends on the ability to localize the already implanted radioac-tive seeds and the most convenient way of achieving this is to use the TRUS probe. However,it is di cult to localize individual seeds on the ultrasound due to the small seed size and highbackground noise from speckles and shadow artifacts in the surrounding tissue[7]. Localizing thestrands is also an issue as the spacer material that make up the majority of the strand give avery dim intensity response.Though seed and strand localization are di cult to accomplish in traditional ultrasound, anovel image enhancement technique developed at the UBC Robotics and Control Laboratory usingaverage-re ected-power imaging has proven to be promising in making this process easier[23].In addition, a new type of brachytherapy strand is now available made from highly acoustically-re ective spacer materials. The special composition of these EchoStrandsTM allows the entire1Chapter 1. Introductionstrand to be visualized on ultrasound images.This project aims to determine if the use of average-re ected-power imaging and EchoStrandsTMcan form the basis for accurate ultrasound strand localization. The ability to localize regularbrachytherapy strands and EchoStrandsTM using traditional ultrasound B-Mode imaging andaverage-re ected-power imaging is also compared.If a signi cant improvement in strand localization is found, subsequent experiments canthen be conducted in a clinical study to determine the full viability of seed localization usingEchoStrandsTM and average-re ected-power imaging.2Chapter 2Brachytherapy2.1 BackgroundIn treating prostate cancer, traditional options have included radical prostatectomy, externalbeam radiation and hormonal therapy, but over the last two decades, brachytherapy has in-creasingly gained acceptance as a minimally invasive treatment option[10]. Brachytherapy canserve both as a complete course of treatment and be complemented by external beam radiationtherapy[24].The most important advantage of brachytherapy is its ability to deliver extremely localizedradiation to speci c targets in the body. This allows much higher doses to be delivered to targettissues than those achievable by external beam radiation therapy[4]. A high dose rate bothdecreases the likelihood of cancer recurrence and treatment time.Brachytherapy is associated with lower morbidity rates and leads to fewer incidents of sexualdysfunction and incontinence as compared to other treatment procedures[4, 24]. A greater preser-vation of sexual potency is also observed from brachytherapy as a great majority of individualscan continue to engage in sexual activities following the procedure[18].Major acute complications from brachytherapy are also extremely rare. Events such as bleed-ing that require transfusion, admission to the intensive care unit and death have not being notedin literature[4].Brachytherapy has existed in some form since the 1960s but it was only in 1985 that themodern method of trans-perineal ultrasound guided brachytherapy was  rst performed by Dr.Blasko and Ragde. Over the past 25 years, technological and procedural developments havegreatly increased the e ciency and quality of the procedure but the basic approach remainsrelatively the same[4].Modern brachytherapy is divided into two stages. First, computerized treatment planningis conducted to determine the proper number, strengths and positions of the radioactive seedsources. Second, the actual seed implantation procedure takes place[11]. The Brachytherapyprocedures presented in the following sections are based on guidelines found in review articleswritten by the American Brachytherapy Association and other research centers[4, 11, 24].32.2. Brachytherapy Planning2.2 Brachytherapy PlanningThe planning stage for the brachytherapy procedure can be done from days/weeks before theimplantation procedure to immediately proceeding it. Planning consists of performing an ultra-sound volume study on the prostate region. The prostate and other organs are then delineatedfrom the volume study images. Seed positions are  nally determined through an optimizationprocedure to give the desired radiation dosage to the target organs.Figure 2.1: To perform the volume study, the TRUS is inserted until its transverse image planeis viewing the apex of the prostate. The probe is mounted on a stepper mechanism that is able towithdraw the probe at 5 mm intervals. This movement is indicated by the gray arrow. Transverseimages are taken at each interval until the base of the prostate is reached. The entire prostatevolume is imaged in this way.The volume study is based on a set of transverse images collected using a trans-rectal ultra-sound (TRUS) probe. The TRUS probe is mounted on a holder that is attached to a steppersupport structure. This stepper is able move the probe at 5 mm step intervals forwards andbackwards. The patient is brought into the operating room and placed in the lithotomy position.The TRUS probe is manual inserted into the patient’s rectum and the support structure is lockedin place. The  nal position of the probe relative to the prostate is shown in Figure 2.1.The stepper is then used to move the probe deeper into the patient’s rectum until the apex42.2. Brachytherapy Planningof the prostate is just visible on transverse image of the ultrasound system. The probe is thenslowly withdrawn using the stepper in incremental steps. For each of these steps, a transverseultrasound image is taken of the prostate region. This is done until the base of the prostate isreached.The set of transverse images forms a three dimensional study of the prostate volume andspecialized software is then used to analyze this image stack. Two dimensional outlines of theprostate, urethra, and rectum are visually determined on each image in the stack. The sets ofcontours that result create three dimensional representations of the organs.Finally, the positions of the radioactive seeds are determined. In brachytherapy, seeds areimplanted via needles and inserted into the prostate parallel to the TRUS probe. Seeds that needto be inserted at di erent depths but at the same position on the transverse plane are insertedusing the same needle. To increase the number of seeds that can be implanted with one needle,certain constraints are applied to where the seeds can be placed.Seeds are made to associate with speci c images in the volume study and the depth of theseeds correspond to the depth of the plane of its associated image. The seed’s position on theimage plane is constrained by a superimposed template on the image. This image template ismade to match a physical needle insertion template used during the implantation process. Theneedle insertion template is  xed in position relative to the TRUS probe and forces needles to beinserted parallel to the TRUS probe (directly into a transverse image planes).The valid positions on the image template correspond to physical insertion holes on the needletemplate. Seeds that are in valid positions on the image template will be able to be deposited inneedles going through the corresponding holes on the insertion template.Constrained by the above factors, seeds are distributed across the volume of the prostate.A dosimetry pro le is constructed from the seed positions which indicates the level of radiationdelivered to di erent regions. Isodose contours are computed from this dose pro le and aresuperimposed onto the organ outlines to determine the degree of radiation exposed to di erentorgans. Manual and automated optimization procedures are then conducted on the seed positionsto obtain the best dose distribution (for more detail on what it means to have the best dosedistribution, consult Section 2.3).A  nal written report, such as the one shown in Figure 2.2, is then created to serve as aguide in implantation process. In the report, needle insertion depth and transverse positioningare determined. The transverse positioning is given in terms of the coordinate system of the seedplacement template while the depth is set based on the depth of the corresponding image planesthat the seed is placed on. Details regarding the number and distribution of seeds within eachneedle are also given.52.2. Brachytherapy PlanningFigure 2.2: In a planning report, the table on the left has needle insertion information. Eachneedle is uniquely identi ed by a number. On the table, each needle’s retraction distance is givenalong with its insertion location on the needle template. Note the positioning on the templateis alphabetically on one axis and numerical on the other. The number of seed for each needle isalso given. On the right, the distribution of seeds in each needle is illustrated.62.3. Seed Placement and Dosimetry Considerations2.3 Seed Placement and Dosimetry ConsiderationsI125 and Pd103 are the primary isotopes used to create brachytherapy seeds. Both radiationsources are X-ray emitters that decay via electron capture. I125 has a photon energy of 28 keVand Pd103 has an energy of 21 keV[24]. The primary di erence between the isotopes is the rate ofdecay with I125 having a half-life of 60 days and Pd103 having a half life of 17 days[24]. However,there is no de nitive evidence to suggest that one is better than the other for the purposes ofbrachytherapy[11].The isotopes deliver extremely localized radiation with a rapid fall-o in energy away from thesource center. Radiation measurements taken in air around an I125 and Pd103 radiation sourceshows more than a 90% fall-o between the doses at 5 mm and 15 mm from the source[24].The localized nature of brachytherapy sources mean changes in their positioning can drasti-cally change the generated dose pro les. This can cause some targeted areas to be under-dosedand others to be over-dosed. This is an important issue as the dose delivered to di erent areasin the target region a ects the success of the procedure and the patient’s quality-of-life.The primary goal in brachytherapy is to deliver enough radiation to the cancerous tissues ofthe prostate to kill all proliferating cancer cells. Cancer cells that are not killed will proliferateagain leading to a recurrence. Studies have indicated that the entire prostate region needs tobe exposed to radiation levels of around 160 Grays in order to minimize the likelihood of cancerrecurrence[20].To guarantee adequate radiation is delivered to the cancerous tissues of the prostate, it mightbe tempting to distribute a set of very high dosed seeds throughout the prostate. However, highradiation exposures to the organs neighboring the prostate can damage them and create adverseand long-term complications.The urethra runs lengthwise through the center of the prostate. High dose delivered to theurethra is associated with increased likelihood of long-term urinary morbidity[19, 22]. To avoidthis, seeds are not implanted in close proximity to the urethra. This limits them to the moreperipheral regions of the prostate[24].High doses of radiation exposed to the rectal walls are associated with an increase in the riskof ulcerations and bleeding, leading to long-term rectal complications[22]. The anterior wall ofthe rectum is situated adjacent to the posterior side of the prostate making it di cult to deliverthe necessary high doses to the periphery tissues of the prostate without exposing the same doseto the wall of the rectum[24]. Care is taken to avoid placing seeds to close to this region.The prostate is also surrounded by neurovascular pedicles and other structures that are re-quired for penile erectile functions. High dose exposure to these tissues can cause damages thatincrease the chance of impotency following the operation [18]. To avoid this, seeds are kept withinthe con nes of the prostate volume as much as possible.Without careful planning, delivering the necessary level of radiation to the cancerous tissues72.4. The Implantation Procedureof the prostate can negatively impact the surrounding tissue resulting in increased risk of post-operative complications. The  nal seed positions determined from the planning process shouldstrike a  ne balance between the goals of killing cancer tissue and sparing healthy tissue.2.4 The Implantation ProcedureThe brachytherapy seed implantation procedure is conducted using the same setup as the one forthe volume study. The patient is once again placed in the lithotomy position and the TRUS isinserted into the patient’s rectum.The TRUS needs to be in the same position relative to the prostate area as it was in the plan,otherwise the clinician will not be able to correctly insert the needles as indicated by the plan.To do this, the ultrasound system is set to actively display transverse images as the TRUSis manually inserted into the patient’s rectum. The positioning of the TRUS is adjusted untilit is able to roughly obtain the same image of the apex of the prostate as in the volume study.This is usually done by matching speci c calci cation structures and organ outlines between theplanning image and the current image. The TRUS is then stepped outwards to determine thecorrelation of the current set images with those from the volume study. The TRUS adjustmentcontinues until the image sets match closely.Once the TRUS is positioned correctly, the needle insertions begin. The needles are insertedpast the insertion template (through the holes at the planned grid positions), through the patient’sperineum and into the patient’s prostate. Since the current image plane depths are matched tothe ones in the volume study, the stepper is used to obtain the transverse image at the plannedinsertion depth. The needle is inserted until it is just visible at this depth and the strand in theneedle is then deposited.The deposition of a strand involves pulling back the hollow cover of each needle while holdingthe central rod in place. Once the hollow needle no longer covers the strand, both the needle andthe central rod are pulled out. This deposits the strand in the prostate.The needle insertion process continues until all the strands are implanted into the prostate.The last step in the operation checks the quality of the implant. This involves determining the nal seed placement and is usually done using a CT scanner. The scanner collects a series ofcross-sectional images of the prostate region. Seeds show up as bright spots on these images whilestrand materials and soft tissue are harder to discern.From these images, the seed positions are identi ed and dosimetry is calculated. The result-ing position and dose information are then compared to the preplan in order to determine theaccuracy of the seed placement and determine any areas that are under-dosed. Reconstructionfrom  uoroscopy images and MRI imaging are alternatives to CT in post-operative analysis[12].82.5. Intraoperative Modi cation2.5 Intraoperative Modi cationThough brachytherapy has been shown to be a valid treatment option with relatively low post-operative complications, the traditional two step process of planning and implantation creates agreat degree of uncertainty in the procedure. These uncertainties are attributed to di erences insetup between the two stages of the procedure as well as errors in the seed implantation process.The actual positions of the seed that are implanted can di er greatly from where they should beas illustrated in Figure 2.3.Figure 2.3: 3D reconstruction of the planned seed positions in a brachytherapy procedure (blue).This is superimposed over the actual implanted seed positions (yellow). The implanted seedpositions are determined using  uoroscopy reconstructionDuring the implantation stage, the clinician has to manually match the relative TRUS toprostate position to what it was in the volume study. This is a very time consuming and inaccurateprocess. Anesthesia applied to the patient during implantation stage can further complicatethis as it relaxes the muscles around the prostate region and alters the size and shape of theprostate[24]. The prostate can also change size in the period between the volume study andimplantation [13].In addition to TRUS positioning errors, inaccuracies in strand placement can account forlarge seed positioning changes from the plan. Patient movement and motion due to respirationcan cause errors in needle to prostate positioning. The prostate can swell due to edema and92.5. Intraoperative Modi cationincrease in size during the course of implantation. The prostate can be deformed by the force ofthe inserting needle and the needle can also be bent by the force of the surrounding tissue[7, 13].As discussed in Section 2.3, an adequate dose of radiation must be delivered to the canceroustissues of the prostate while exposure to other functional organs surrounding the prostate shouldbe minimized. However, the localized nature of the radiation from the brachytherapy sourcesmean any errors in placement can cause planned high dose areas to not receive enough radiationand planned low dose areas to receive too much radiation.To reduce these errors in the treatment procedure, the American Brachytherapy Societyrecommends[13]:"[Striving] for on-line, real-time intraoperative dosimetry to allow for adjustment inseed placement to achieve the intended dose."In the ideal situation described above, a dynamic treatment plan is created in real-time byheavily modifying the plan created in the planning stage. Actual implanted seed or strandpositions are determined after each needle deposition. The radioactive source positions are thenfed into a computer algorithm that constructs, in real-time, an accurate dosimetry pro le of theprostate volume. This process is called real-time dosimetry. Based on this up-to-date dosimetrypro le, new strands can be added and existing strand positions can be modi ed to compensatefor any errors in dose delivery[13].Current intraoperative planning procedures do not fully reach the ideals set by the AmericanBrachytherapy Society. To reduce setup di erences, some clinicians conduct the planning stageof brachytherapy immediately prior to the implant stage. In this, the same setup is used in bothstages and clinicians not longer have to match up the TRUS positions. However, this puts a tightconstraint on the planning process and can extend the operating time of the procedure[13]. Thisprocess is called "intra-operative preplanning".To account for needle  exion and movement of the prostate due to needle insertion, certainprocedures have tried to intraoperatively detect the path of the needle as they are inserted.In these procedures, a set of needles are inserted and then imaged by a sagittal image sweep,conducted by spinning the TRUS probe around its axis. The sweep is used to reconstruct theneedle positions in three dimensional space and can be used to determine any needle insertionerrors[13, 25].The two modi ed brachytherapy protocols described above manages to remove some uncer-tainty in the procedure, but does not fully solve the problem. Even being able to localize theneedles does not allow us to localize implanted strands as the seeds and strands still move duringthe deposition process and are often not deposited following the needle path[13].The inability to accurately localize radioactive sources prevents the creation of accurate real-time dosimetry pro les. This, in turn, hinders the ability to detect and compensate for tissueareas that are receiving inadequate dosage.102.5. Intraoperative Modi cationFigure 2.4: In both transverse and sagittal TRUS images, implanted brachytherapy seeds intissue is extremely hard to discern due to the noisy environment. The implanted seed is circledin red in the images above. DataCredit : Xu;UBCRCLAttempts had been made to try to localize planted seeds using the TRUS probe. Since itis already used to guide needles insertions, it is a convenient medium to use in attempting tolocalizing radioactive sources. However, an ultrasound image of the prostate area is extremelynoisy. Numerous calci cation sites, speckles and shadow artifacts are present in these images,as can be seen in Figure 2.4. Small seeds tend to show up very poorly on traditional TRUSultrasound images [8, 23]. The strands provide a bigger pro le for detection but parts of themdo not generate a strong intensity response on ultrasound images (see Section 2.6).More advanced ultrasound techniques such as Doppler Ultrasound and vibro-acoustographyhave been used to enhance the contrast between the seed and background noise. However, thesetechniques require the addition of specialized equipment making them inconvenient for a tightlyscheduled procedure [8, 9].Other than ultrasound, MRI and X-ray  uoroscopy provides excellent seed localization abil-ities but the extra imaging equipments impart a large overhead. The high cost associated withMRI imaging makes it hard to incorporate into brachytherapy. X-ray  uoroscopy is much cheaperbut it can’t visualize the prostate contours meaning that the positions of the imaged seed relativeto the prostate can’t be directly determined[3, 15].112.6. Regular and EchoStrandsTM2.6 Regular and EchoStrandsTMSeeds loaded into brachytherapy needles come in two di erent forms, loose seeds and strandedseeds. Both types carry distinct bene ts and drawbacks and are often used in conjunction in asingle brachytherapy procedure.Loose seeds come in a set of individual seeds with spacer materials of di erent length. Basedon the requirements, the seeds are individually loaded into insertion needles and spaced out atspeci c intervals by a spacer material. Once the needle is loaded with the necessary number ofseeds interspaced by the correct spacers, it is ready to be used.Loose seeds carry the bene t of allowing new needles to be created intraoperatively withthe desired number and depth of seeds. This allows for great  exibility during the operation asclinicians can active modify the plan and creates new needles that re ect the modi cations.The alternative to loose seeds is stranded seeds or strands. Strands consist of seeds suturedtogether along with spacers into a single long structure that is loaded into the needle as a whole.The entire strand is then deposited into the patient’s prostate. The strands are often made bythe manufacturer before-hand and must be ordered during the planning stage. This gives theclinician less  exibility during the procedure but makes the insertion process faster. Strandedseeds also prevent seed migration from occurring.Seed migration occurs when loose seeds are inadvertently implanted outside the venous plexussurrounding the prostate gland causing them to be carried o by blood vessels to the pelvis andeven the lung[4].Figure 2.5: EchoStrandsTM (top) have small gas  lled micro-bubbles within its spacer material(spacer material is shown in blue). The spacer material of a regular strand (bottom) has a uniformcomposition.Traditional spacer material found in strands and with loose seeds is made from a uniformbio-absorbable suture material composed of braided Vicryl (polyglactin 910) and is thermallysti ened[24]. In strands, this material is also used to encase the seeds. This material is requiredto be bio-absorbable as the entire strand is permanently implanted within the prostate. The122.6. Regular and EchoStrandsTMlong strands will cause long-term discomfort in patients if the spacer material holding the strandtogether does not degrade over time.The bio-absorbable requirement of the strand material limits the selection of materials thatmake these strands. The bio-absorbable materials that are currently available show up poorly inultrasound, making it hard to visualize entire strands accurately.A new form of strand is now available called EchoStrandTM (See Figure 2.5). The spacermaterials of these EchoStrandsTM contain specially embedded gaseous micro-bubbles that in-crease the ultrasound intensity response of the strand. These micro-bubbles are  lled with gas,which is generally a very poor medium for ultrasound propagation. This results in most incomingultrasound beam being re ected at the boundaries of the gas  lled micro-bubbles, making themextremely re ective.The use of micro-bubbles as contrast agents in ultrasound has been an active point of researchin recent years in the  eld of contrast enhanced ultrasound. This technology is used mainly inthe analysis of the vasculature of large organs. The micro-bubbles in used in those experimentsare enclosed volumes of gas surrounded by a shell of organic material such as albumin. They arethen injected into the blood stream to be detected by the ultrasound[1, 17].13Chapter 3Ultrasound Image Analysis3.1 Basics of Ultrasound ImagingIn ultrasound imaging, a transducer both emits and collects sound waves through the use of itspiezoelectric crystals. A piezoelectric crystal undergoes high frequency vibrations in response toelectrical signals, producing ultrasound in the process. The ultrasound waves are focused into anarrow beam directed at the tissues being imaged. The sound waves exert varying pressure onthe particles in the medium transmitting their energy and causing these particles to vibrate inplace. The sound energy is continuously propagated by the transfer of this energy from particleto particle[21].Figure 3.1: The re ected ultrasound echoes are saved in the form of a radio-frequency (RF) signalplotted on a time scale. High amplitudes on this plot correspond to re ective boundaries in themedium with the position along the plot corresponding to distance to the re ective boundary.143.1. Basics of Ultrasound ImagingEmitted ultrasound energies propagate through a medium until they encounter an acousticboundary. These boundaries form between two mediums of di ering densities. At these bound-aries, a portion of the ultrasound energy is re ected back as echoes which are then picked up bythe original transducer. The crystals of the transducer then converts and records the receivedsound energies into a electrical signal (as shown in Figure 3.1)[21].The total strength of the echoes received at a speci c time is recorded as a time-based ra-diofrequency (RF) signal. Since echoes from greater depths take longer to travel back to thetransducer, received echo time is directly proportional to the depth of the echo’s correspondingre ective boundary[21].Each piezoelectric crystal is designed to project ultrasound in a narrow beam, detectingre ective boundaries at various depths along a single direction. The transducer uses a lineararray of these crystals to collect data on a plane[21]. There are typically two sets of these arrayson a TRUS probe, allowing it to collect both transverse and sagittal images (See Figure 3.2).Figure 3.2: The TRUS probe can image two image planes. The transverse image plane isgenerated by data collection from a crystal array that runs radially around the tip of the TRUS.The sagittal image plane is generated by a crystal array running along the length of the TRUS.The  nal ultrasound image is composed from a set vertical scan-lines. Each scan-line corre-sponds to the RF signal generated by one of the crystals in the array. The pixel intensities alongeach scan-line are relative to the RF signal strength received from echoes at speci c depths.The raw RF signal varies over an extremely large range. In order to  t it into a displayable153.2. Image-Based Strand Localization Considerationspixel value, the RF intensity is  rst  ltered and compressed to be within the intensity range ofnormal tissue. The output image is the familiar B-Mode ultrasound image.3.2 Image-Based Strand Localization ConsiderationsThe goal of this project is to determine how well our methods work at localizing implantedbrachytherapy strands in three dimensional space.Strands can be localized on image planes by determining its position on the image. However,when there is an image stack and the strand appears on several images in this stack, it is importantto determine on which image plane the strand corresponds to. This is discussed in Section 3.2.1.The orientation of the strand is also expected to in uence the ability to localize these strands.The interaction between ultrasound image intensity responses and the strand orientation is dis-cussed in Section Localizing to Image PlanesIn order to localize the implanted strands using ultrasound, its positioning needs to be accuratelydetermined across all axis in three dimensional space. However, ultrasound images are in twodimensions and in order to reconstruct a three dimensional region of interest using them, a seriesof consecutive ultrasound image slices must be taken.In brachytherapy, these image slices are collected by setting the TRUS probe to image sagit-tally. The probe then rotates around its axis (shown in Figure 3.3) collecting an image aftera certain degree of rotation. The image set can then be used to reconstruct a sector volumerepresentation of the imaged region.Each of these ultrasound images correspond to an image plane with known positioning relativeto the TRUS. Both the speci c image plane that the strand corresponds to and its positioning onthat image plane needs to be determined before it can be localized in three dimensional space.The position of the strand on the image plane can be determined simply by manually orautomatically segmenting the strand from the background based on its intensity response. De-termining which image plane the strand corresponds to is more di cult.During its travels through the medium, individual ultrasound beams tend to be de ected bydi erent the particles within the medium. This means that the emitted ultrasound beams willbe de ected in di erent directions and the transducer receives incoming ultrasound re ectionssources that are not directly on the imaging plane[21]. In terms of strand localization, this resultsin strand that do not directly lie on the image plane still giving an intensity response.Fortunately, the intensity responses of strands that are not directly on the image plane areweaker than those from strands that are. In addition, the further away the strand becomes fromthe imaging plane, the weaker its response becomes. This property allows the determination ofthe corresponding image plane of a strand with a degree of uncertainty.163.2. Image-Based Strand Localization ConsiderationsFigure 3.3: The strand positioning can be determined by collecting a set of sagittal images asthe TRUS is rotated around its axis. The set of images can then be used to reconstruct thesector volume around the strand. However, one major issue is determining which image planethe strand is actually on.For the purpose of localization, it is desirable to receive a large intensity response when thestrand is directly on the imaging plane and a rapid fallo in intensity as the strand is furtheraway from the imaging plane. Once this intensity response versus distance to imaging plane isknown, strands that are on the imaging plane and strands not on the plane can be separated. Athreshold value can be set such that the strand with intensity above the threshold is associatedwith the image plane while those below belong to another image plane. With a rapid fallo ofintensity, we can more accurately make this distinction taking into account natural variation instrand intensity.In the situation where the strand intensity response does not have a rapid fallo , it becomesmuch harder to separate between strands that are close to the image plane and those that are faraway. A greater degree of uncertainty is associated with strand positions in this case.There will always be a degree of uncertainty when trying to associate an intensity responseto a particular image plane. However, large drop-o s in intensity as the strand moves away fromthe imaging plane makes it easier to do so.3.2.2 E ects of Strand Orientation on Ultrasound Re ectanceOne of the major sources of error in seed and strand placement is needle  exion. As the needle isinserted into the patient’s body, it is de ected through the interaction of the surrounding tissuewith the tapered needle tip. When such a needle then deposits its strand, the strand is depositedin a bent shape and at an angled orientation[2].173.2. Image-Based Strand Localization ConsiderationsImaging both seeds and strands on ultrasound at di erent orientations will give di erentintensity responses. This has to do with how ultrasound re ection is generated on these strands.There are two types of re ection in ultrasound. Specular re ection occurs with a relatively largeand smooth acoustic boundary while non-specular re ection occurs with a smaller and irregularboundary.Figure 3.4: In specular re ection (top), the incoming ultrasound beams are re ected from thesurface in a very uniform manner. This occurs on smooth re ective boundaries. In non-specularre ection (bottom), the incoming ultrasound beam is scattered in all directions when in contactwith an uneven re ective boundaryA simple law governs specular re ection. The direction of the re ected ultrasound beam ison the opposite side of the normal in relation to the incident beam with the angle of incidenceequal to the angle of re ection[21]. Based on this, the chance of the transducer that emittedthe ultrasound beam receiving its echo is expected to be higher as the angle of incidence andre ection decreases. When the beam incident ultrasound beam is perpendicular to the surfaceof the boundary, it is expected that the echo will go straight back to the transducer. This isillustrated in Figure 3.4.Non-specular re ections or scattering does not obey any simple laws of re ection. The roughsurfaces that cause non-specular re ections re ect ultrasound beams back in many di erent di-rections. These re ections tend to be much weaker than specular ones but are not a ected by183.3. Average-Re ected-Power Imagingchanges to the surface orientations as illustrated in Figure 3.4.Ultrasound seeds are long cylindrical objects. The length of each seed is much greater than thediameter of its cross-sectional area. This meaning most incoming ultrasound beams hit along itslengthwise surface. These surfaces are extremely smooth resulting in mostly specular re ections.When we change the orientation of the seed, we change the orientation of the seed’s lengthwisesurface. A very high intensity response is expected for seeds orientated with its length perpendic-ular to the incoming ultrasound beam as the ultrasound beams are echoed back in the directionof their origin. The intensity is expected to decrease as the seed is orientated in away from thisangle which directs ultrasound echoes away from their source. This e ect is seen in B-Modeimages as well as in average-re ected-power images [2]. Figure 3.5 illustrate the e ect in the laterimage type.Figure 3.5: A set of average-re ected-power images of brachytherapy seeds of di erent orienta-tions implanted in a phantom. The intensity of the cylindrical implanted seed is seen to decreaseas they are orientated to steeper angles. DataCredit : Xu;UBCRCLIn this experiment, the investigation is conducted on strands and not seeds. Though thecomposition of the strand is di erent than that of the seed, the overall geometry of the strandis still the same. The strands are still cylindrical with most of ultrasound re ectance occurringalong its lengthwise surface. It is expected that the same intensity fallo will also occur in strandsas it was seen for seeds.This means that any intensity response or contrast analysis on the strands needs to be doneover a range of di erent orientations to account for the intensity fallo .3.3 Average-Re ected-Power ImagingA lot of contrast is lost when the A-lines signals are converted into B-line intensity dots. Toovercome this problem, the average-re ected-power imaging technique used in this project di-rectly generates high contrast images from the information in the A-lines without any form ofcompression.This technique is developed by Xu Wen at the UBC Robotics and Control Laboratory andhas been used in previous studies to better localize implanted brachytherapy seeds. The imaging193.3. Average-Re ected-Power Imagingtechnique was found to greatly enhance the intensity response of the seeds and increase theircontrast over background noise, resulting in better localization[23].In this imaging technique, the A-line is  rst divided into a number of overlapping blocks. Foreach of these blocks, the amplitude of each of discrete signal value in these blocks are averagedto generate a single average intensity response. This averaging can be done over both the timedomain and the frequency domain. This process is illustrated in Figure 3.6.Figure 3.6: In average-re ected-power imaging, the amplitude line is divided up into shortoverlapping blocks. The intensity within each of these blocks is averaged over the time domainor the frequency domain. The averaged value for each amplitude line then forms a scan-line inthe average-re ected-power image.The calculation of the average over the time domain is conducted in a relatively straight-forward manner. Within each block, the squared modulus of the discrete intensities of the RFsignal is averaged using Equation 3.1. The average intensity for the block at depth d, indicatedby PA(d), is calculated from the discrete intensity signal values found at the di erent positions,k, along the block indicated by xd(k).203.3. Average-Re ected-Power ImagingPA(d) =PNk=0jxd(k)j2n (3.1)Parseval’s Relation states that the total energy in an n-point frequency spectrum of a signalis equal to its total energy in the n-point time sequence[14]. Following this relation, as illustratedin Equation 3.2, the average intensity for the block can also be calculated over the frequencydomain.N 1Xn=0jx[n]j2 = 1NN 1Xk=0jX[k]j2 (3.2)To average the block of signal over the frequency domain, the signal in each block has to be rst converted into the frequency domain. Fast Fourier Transform (FFT) is used to convert theoriginal signal into a Fourier spectrum which is a representation of which frequencies are presentin the original signal.However, the Fourier Transform tend to give a non-zero responses for frequencies close to thetrue signal frequency. These "spectral leakages" will interfere with the signal averaging process.To prevent spectral leakage, the Hamming Window, given in Equation 3.3, is  rst multiplied tothe signal. This window function serves to minimize the nearest frequency responses to the actualsignal frequencies. This reduces spectral leakage in the resulting Fourier spectrum.w(n) = 0:54 0:46cos( 2 nN 1) (3.3)The squared modulus of the Fourier Spectrum is then averaged using Equation 3.4, wherePd(fk) is the squared modulus of the magnitude of the k’th frequency component in the 2N-pointpower spectrum of the segment. Only N points are used since the spectrum is symmetric abouthalf of the sampling frequencies. These values are summed to calculate the averaged intensityvalue at depth d.PA(d) =PNk=0Pd(fk)(N + 1)2 (3.4)Although calculations in both domains can give equivalent results, the computation in thetime domain is much faster since it does not involve FFT. Average over the frequency domainallows the sub-sampling of intensity responses over a set range of frequencies. This allows theremoval of high and low frequency noise.Preliminary tests performed on sets of imaged strands found no improvements in data clarityor signal to background contrast when the frequency range was limited using the frequency domainmethod. This is attributed to the fact that the radio-frequency intensities of the background noiseis much lower than that of the strand. The removal of these noise has little impact on the  naldata. As a result, the average-re ected-power calculations will only be done in the time domain213.3. Average-Re ected-Power Imagingfor this experiment to take advantage of the much shorter computation time.22Chapter 4Quantitative Strand IntensityResponse Measurements4.1 Experiment MethodsThe  rst part of this experiment aims to quantitatively compare the average-re ected-power imageintensity responses from both EchoStrandsTM and regular strands under a variety of di erentstrand orientations and distances to the ultrasound image plane. The quantitative results fromthis allow the determination of the e ects of strand orientation on strand image intensities as wellas the ability to attribute a strand to a speci c image plane. This requires the ability to bothrotate the strand into di erent orientations and rotate the trans-rectal ultrasound probe (TRUS)so that its image plane sweepes across the strand.The experiment is done on both types of brachytherapy strands. The regular strand is tested rst, followed by the EchoStrandTM. Both strands are equal in size with a cross-sectional diameterof 0.86 mm and a length of 30 mm. Both strands consistes of 3 seeds of length 4 mm. Two aresituated at either ends of the strand while the third is placed in the middle. These are separatedby spacer materials of length 15 mm.An Ultrasonix 500 RP PC-based ultrasound system with a biplane TRUS transducer is usedin this experiment (shown in Figure 4.1). The system allows the simultaneous collection of bothB-Mode image and raw radio-frequency (RF) data.An acoustically transparent environment with very little background noise is required foraccurate quanti cation of the strand measurements. This is achieved by submerging both theimaged strand and the ultrasound transducer in a large bucket  lled with water. Water is avery conducive medium allowing ultrasound beams to traverse through with minimal scattering,producing a silent background.The strand is suspended in water by a specially designed strand holder. The holder, which isshown in Figure 4.2, is made from three  at pieces of stainless steel. The largest piece consists ofthree arms. The two smaller pieces served to wedge the ends of the strand between themselves andtwo of the arms of the larger piece. This suspends the strand between the two arms preventingany impedance to the incoming ultrasound beams. The three pieces of metal are held togetherby nuts and bolts.To suspend the strand holder in water and also allow the strand to change orientations, the234.1. Experiment MethodsFigure 4.1: The Ultarasonix 500 RP PC-based ultrasound system with an Ultrasonix biplaneTRUS transducer(inset).last arm of the holder is attached to a large metal sca old.This sca old has a U-shaped structure with a short horizontal piece that attaches to two longvertical arms. It is constructed from a long, thin piece of metal and, when folded, has a width of7.5 cm. Each arm is 27.5 cm in length and the central portion is 16 cm long.One of the arms is the attachment site of the strand holder and is submerged in water whilethe horizontal center piece of the sca old straddles over the side of the water container. Theother arm is just outside container and attaches to an upright Parker Automation M100000Rotary Positioning Stage clamped to laboratory bench. The sca old ensures that when therotary positioning stage is rotated over a certain degree, the strand holder is also rotated overthe same range. The position of the strand holder along the arm of the sca old is calibratedsuch that the axis of rotation of the strand on the strand holder is the same as that of the rotarypositioning stage. The entire setup is shown in Figure 4.2.The trans-rectal ultrasound probe (TRUS) is mounted on a specially designed cradle systemthat attaches to a motorized encoder. The encoder is able to rotate the cradle around its axisand detect the degree of this rotation. Both the cradle and the encoder are mounted onto a244.1. Experiment MethodsFigure 4.2: The strand holder is attached to a large metal sca old. The holder and one armof the sca old are submerged in water while the crosspiece straddles over the side of the watercontainer. The other arm is outside the container and is attached to an upright rotary platform.When the platform is rotated, the sca old is also rotated, causing the strand holder with thestrand to rotate as well. The axis of rotation of the strand is made to match that of the rotarystage (red line).254.1. Experiment Methodsbrachy-therapy platform which attaches to the laboratory bench. The basic setup is shown inFigure 4.3.Figure 4.3: The TRUS probe is mounted on a specially designed cradle system attached to amotorized encoder device. The encoder is able to rotate the cradle and the probe around theiraxis. Both the cradle and the encoder are mounted onto a platform that is  xed to a bench.The platform is then manually adjusted to place the TRUS at an angle, submerging theimaging portions of the device in the water container while maintaining the cradle, encoder andthe platform over the water surface. The TRUS is positioned so that it is roughly right on top ofthe strand. Precision translational and rotational controls built into the platform are then usedto adjust the transducer such that the transducer’s incident beam directly hit the entire lengthof the strand. The  nal position of the TRUS is illustrated by Figure 4.4.To begin the experiment, the strand is oriented to be perpendicular to the direction of theincoming ultrasound beam. This is done by rotating the rotary positioning stage until the strandappears horizontal on the output ultrasound image. This results in the long axis of the TRUSbeing parallel to the strand and is set to be the zero degree strand orientation angle.The image plane from the TRUS probe is made to sweep across the strand by rotating theTRUS along its axis. Zero degree for the sweep angle is set to be when the ultrasound beamdirectly hit the strand. The TRUS is rotated to sweep its beam from -20 degrees to 20 degree.Custom designed software controls this rotational process and collects a series of B-Mode and264.2. Image Analysisradio-frequency images. These image series are then saved to  le. The angle of rotation of theTRUS is encoded into the header of the corresponding image in the  le.After the initial TRUS probe sweep at zero strand orientation, the strand is reoriented to 2degrees. This is done by rotating the rotary positioning platform 2 degrees counter-clockwise.The same sweep procedure is repeated for this new strand orientation. In total, 12 orientationsare tested at every 2 degrees from 0 to 22 degrees.Figure 4.4: To image the strands, the tip of the TRUS is submerged in water and positionedright on top of the strand. The sagittal image plane directly intersects the length of the imagedstrand. When the TRUS is rotated along its axis (red arrow), the sagittal image plane is sweptacross the strand (white arrow)4.2 Image AnalysisThe raw RF sagittal image data are  rst converted to average-re ected-power image data beforethe analysis took place. Each of the raw RF images compose of 176 scan-lines with length of5696 pixels. The raw RF A-lines are split into a series of overlapping blocks. These blocks havea length of approximately 0.4 mm (137 blocks) with approximately 80% overlap. The outputaverage-re ected-power images are reduced to 176 scan-lines with length of 80 pixels.To account for both the intensity of the strands and the small variations in intensity along274.3. Resultsthe strand, a series of 10 rectangular regions of interests are taken consecutively along the lengthof the strand material (shown in Figure 4.5). These ROIs are made sure to only sample intensityresponses from the strand spacer material and not from the seeds in the strands. The ROIs are6 pixels wide and 8 pixels high which correspond to a sample dimension of 0.9 mm by 3.2 mm.Figure 4.5: The intensity response of a strand in an ultrasound image is sampled by creating tenROI along the length of the strand. An integral of intensity is then calculated for each sample.The above image shows the sampling for the regular strand in zero orientation (top) and fourteendegree orientation (bottom) with the set of ROIs represented by yellow rectangles.The height of the ROIs is made to be roughly two times the width of the actual brachytherapystrand. This serves to compensate for minor changes in distance between the ultrasound sourceand the strand as the TRUS probe is rotated. The increased height allows the strand to be inthe set of ROIs at all times during the TRUS sweep.The integrated optical density (IOD) for each of these ROIs is then computed. This is done bysumming up all the intensities of the pixels in each ROI. The mean and standard deviation of theset of IOD values from all ten ROIs are calculated giving the desired quantitative measurementof strand intensity.4.3 ResultsTo analyze the intensity response of the strand in terms of their distance to the ultrasound imageplane, the intensity response of the strand is plotted against the angle of the TRUS roll. Separate284.3. Resultsplots are done for TRUS image plane sweeps for all the di erent strand orientations. These areshown in Figure 4.6 and 4.7.From the plots, both regular and EchoStrandTM give similar intensity pro les at low seedorientations. Both give a high intensity response when the strand lies directly on the ultrasoundimage plane with a rapid fall in intensity as the image plane moved away from the strand.At high orientations, however, the EchoStrandTM still maintains a sharp intensity fallo pro le, but the regular strands  attens out. At these orientations, the initial intensity responseof the regular strand when the ultrasound beam is incident on the strand is low and there is amuch shallower intensity fallo as the ultrasound beam moves away from the strand.To observe the relationship between strand intensity response and the orientation of thestrand, images of the strand at all di erent orientations needs to be analyzed. We want to selectfrom the beam sweeps the image the corresponds to when the strand is directly on the imageplane. This is the image that corresponds to the peak of the beam sweep pro le which occurs atthe zero degree sweep angle.The set strand images at zero degree sweep angle for both regular and EchoStrandTM atdi erent orientations are shown in Figure 4.8 in B-Mode and in Figure 4.9 in average-re ected-power.Visual inspection of the B-Mode images indicates that the intensity responses of both strandtypes are roughly equivalent at low angled orientations. As the strand orientation angle increaseshowever, the intensity and contiguity of the regular strand rapidly decreases. The EchoStrandTM,on the other hand, experiences decrease in intensity but maintains its relative contiguity.The average-re ected-power images follow the same general trend of the B-Mode. The con-tiguity and intensity for the regular strand decreases at a greater rate than the EchoStrandTMas the strand orientation angle increases. Note that a greater range of intensity di erence can beseen in the average-re ected-power images than in the B-Mode images.The measurements of the IOD of ROIs along strands on these images are shown in Figure4.10. The quantitative data supports our visual conclusion. The intensity of the strand falls o rapidly as the angle of the strand orientation increases. Overall, the EchoStrandTM gives a betterintensity response than the regular strand, though not to a statistically signi cant degree.294.3. ResultsFigure 4.6: Data analyzed for strands in average-re ected-power images. The plots for the meanof integrated optical density (IOD) of ROIs along the length of the strand versus the angle of thebeam sweep for strand orientations 0 degrees to 10 degrees. The TRUS is rolled from -20 degreesto 20 degrees across the strand. Its sagittal image plane directly hits the strand at 0 degrees.Overall, the strand gives the strongest responses at zero degree roll angle, when the strand isdirectly on the image plane. As the image plane is oriented away from the strand, the intensityresponse falls o .304.3. ResultsFigure 4.7: The plots for the mean of integrated optical density (IOD) of ROIs along the lengthof the strand versus the angle of the beam sweep for strand orientations 12 degrees to 22 degrees.The TRUS is rolled from -20 degrees to 20 degrees across the strand. Its sagittal image planedirectly hits the strand at 0 degrees. Overall, the strand gives the strongest responses at zerodegree roll angle, when the strand is directly on the image plane. As the image plane is orientedaway from the strand, the intensity response falls o .314.3. ResultsFigure 4.8: B-Mode images of short strand segments orientated at the indicated angles324.3. ResultsFigure 4.9: Average-re ected-power images of short strand segments orientated at the indicatedangles334.3. ResultsFigure 4.10: Average-re ected-power means of integrated optical density (IOD) of ROIs alongthe length of the strand are plotted against the strand orientation. The image being sampled isthe one that gives the peak intensity output in the beam sweep which corresponds to when thestrand that is directly on the plane of the TRUS sagittal image.34Chapter 5Contrast to Noise Analysis5.1 Experiment MethodsThe second part of the experiment aims to directly compare the e ectiveness of the average-re ected-power imaging in contrasting both the regular and EchoStrandsTM against backgroundnoise over traditional B-Mode ultrasound imaging.A cellulose phantom is constructed in order to create a noisy medium simulating real tissue.The phantom has a rough dimension of 5 cm by 12 cm with a depth of 1.5 cm. The compositionand their relative proportions are shown in Figure 5.1. Of the ingredients involved, the agar,gelatin and glycerol serve to hold the structure of the phantom while the bleach prevents bacteriafrom growing on the phantom. The cellulose particles are suspended within the phantom mixture,creating the noise on the ultrasound image.Figure 5.1: Relative proportions of materials needed to create 100 g of the cellulose phantommaterial used in this experiment.The phantom components are combined in a beaker which is heated on a hot pad and con-stantly stirred with a magnetic stirring strip. Once the mixture reaches 90oC, it is then allowedto cool while still being stirred.When the mixture is cooled to 40oC, half of the mixture is then poured out slowly into asmall plastic box. This box serves as the mold for the phantom. The box is put into the fridgefor 10 minutes allowing the mixture inside to cool and solidify. The half of the mixture that is355.1. Experiment Methodsstill in left the beaker is kept to a constant 40oC temperature by the heating pad.After the phantom material in the box solidi es, it is removed from the fridge. An EchoStrandTMand a regular strand are placed on the solidi ed surface of the phantom at opposite ends. Theremaining mixture in the beaker is then poured into the box completely submerging the strandsand embedding them in the center of the phantom. The phantom is then cut in two to createtwo phantoms with a single strand in each.Embedding the strand in this manner causes the phantom to be formed around the strand.This prevents any air bubbles from being trapped inside the phantom which might occur if thestrand is inserted using needles. Air bubbles interfere gives extremely intense intensity responsesand impede our ability to accurately measure the intensity responses of the strands.The setup for this part of the experiment, shown in Figure 5.2 is very similar to the  rst. Thesame ultrasound system, transducer and strands used in the  rst part of the experiment are usedonce more. The head of the TRUS and the phantom is submerged in water to allow ultrasoundbeam to travel unimpeded from the transducer to the phantom.Instead of suspending the strand in water, however, the entire phantom is mounted on a metalplatform which is then attached to the same sca old used in the  rst experiment. The platformperforms the same role as the strand holder. When the rotary platform on the other arm of thesca old rotates to a certain degree, the platform is also rotated. This adjusts the phantom andthe strand inside to a new orientation. This action is illustrated in Figure 5.2.The trans-rectal ultrasound probe (TRUS) is manually positioned to be right on top of thestrand. Precision translational and rotational controls built into the platform are then used toadjust the positioning of the transducer such that the entire length of the strand is incident tothe transducer’s image plane.To begin the experiment, the phantom and the strand inside are oriented such that theyare perpendicular to the direction of the incoming ultrasound beam. This is done using therotary positioning stage. This sets the long axis of the TRUS to be parallel to the strand andis de ned again as the zero orientation angle. No image plane sweep is conducted for this partof the experiment. Instead, the TRUS simply collects a single frame of both B-Mode and rawradio-frequency (RF) sagittal data.Once the images are collected, the strand is reoriented to 2 degrees orientation by rotating therotary positioning platform counter-clockwise. New B-Mode and RF sagittal images are takenat this orientation. This is done for strand orientations 0, 2, 4, 6, 8, 10, 12, 15 and 20 degrees.Fewer orientations are sampled in this part of the experiment as the results from the  rst partindicates very little intensity response change between 15 and 20 degrees orientations.365.1. Experiment MethodsFigure 5.2: In this experiment, the phantom is placed on a metal platform that is attached toa metal sca old which is attached to a rotary platform. Rotating the rotary platform causes thephantom and the strand inside to change their orientation. The axis of rotation of the phantomand the rotary platform is made to line up. The TRUS probe is placed right on top of thephantom in order to image the strand inside.375.2. Image Analysis5.2 Image AnalysisSimilar to the  rst part of the experiment, raw radio-frequency sagittal image data are convertedto average-re ected-image data. The radio-frequency A-lines are split into a series of overlappingblocks with length of approximately 0.4 mm (137 RF samples) with approximately 80% overlap.A certain level of contrast must exist in order to successfully distinguish the strand frombackground noise. A quanti able value is needed to re ect the degree of contrast. This is thecontrast to background noise ratio (CNR).The intensity of the strand is set to be the targeted signal response. Similar to the  rst partof the experiment, a series of 10 regions of interest are taken consecutively along the length of thestrand spacer material to sample this intensity. The sizes of these ROIs are much smaller thanthose used in the  rst part of the experiment. This serves to limit the ROIs to only encompassingthe strand. These ROIs are 6 pixels wide and 4 pixels high which correspond to a sampledimension of 0.9 mm by 1.6 mm.The background response is set to be the intensity response of the phantom material. A largerectangular region of interest is sampled as the background response by selected an area of thephantom that has a rough size of 20 pixels by 20 pixels, corresponding to a physical size of 3 mmby 8 mm.A signal contrast-to-noise ratio (CNR) is then calculated using Equation 5.1. This equationcalculates a separate CNR value for each ROI selected along the strand. The CNR value is acommon quanti cation to use when determining the ability to discern di erent structures in theultrasound [16].CNR = ms mb 2b(5.1)The factor ms is the mean in intensity of the pixels within a ROI sampling the strand. Thefactors mb and  b are the mean and standard deviation of the pixel intensities from the largeROI sampling the phantom. Each ROI along the sampled strand gives a separate CNR value.The mean and variance for the CNR values for the set of ROI for a single strand are calculatedat the end. Note that the minor variation in strand intensity is not factored into this equation asaverage-re ected-power intensity responses vary in several orders of magnitude than respectiveresponses in B-Mode images.These CNR calculations are done for both B-Mode images and average-re ected-power imagesof regular strands and EchoStrandsTM.5.3 ResultsThe B-Mode images of both regular and EchoStrandsTM in phantom at di erent strand orien-tations are shown in Figure 5.3. It is observed that the contrast between the strands and the385.3. Resultsbackground noise of the phantom decreases as the strand is oriented at greater angles. The theregular strand’s intensity decreases more rapidly as the strand orientation changes in comparisonto the EchoStrandTM. It is discernable over a much smaller range of strand orientations thanthe EchoStrandTM. The change in strand intensity is minimal over the di erent orientations butthe contiguity of the structure drastically decreases structure.Figure 5.3: B-Mode images of short strand segments in phantom orientated at the indicatedanglesFigure 5.4 shows the average-re ected-power images for both regular and EchoStrandsTM atdi erent orientations. Similar to the results in the B-Mode, the EchoStrandTM has better contrastand is more discernable over a greater range of strand orientations than regular strands. Thereis a drop in intensity as the strand is oriented at greater angles as well as a drop in contiguitybut not to the degree found in B-Mode images.The regular strand disappears for orientations greater than 15 degrees but the EchoStrandsTMare still visible up till 20 degree orientation in the average-re ected-power images.The logs of the contrast-to-noise (CNR) ratios are plotted in Figure 5.5. The output agreeswith our observations as there the CNR values for average-re ected-power images are muchhigher than traditional B-Mode imaging. In both imaging mediums, the CNR values decreasewith increases angle.The di erence of CNR values between the strands in the B-Mode output is relatively similar395.3. ResultsFigure 5.4: Average-re ected-power images of short strand segments orientated at the indicatedanglesthroughout though the EchoStrandTM gives a slightly better response at non-parallel orientationsthan regular strands. The CNR for the average-re ected-power images shows more di erencebetween the two strand types. At orientations lower than 10 degrees, the CNR values are relativelyon par with each other. At greater than 10 degree orientations, however, the EchoStrandTM isstill able maintain a high CNR ratios while the regular strand’s CNR is almost negligible.The result of the CNR analysis agrees with the visual inspection of the images. Average-re ect-power imaging gives a much better contrast against background noise over B-Mode imag-ing. The EchoStrandTM can be better contrasted against background noise than regular strandsespecially at non-parallel orientations.405.3. ResultsFigure 5.5: Log of contrast-to-noise (CNR) ratio plotted against the strand orientation fordi erent imaging methods and EchoStrandsTM and regular strands.41Chapter 6Discussions, Conclusions and FutureWork6.1 DiscussionsImaging Methods Based on the results from the contrast to noise analysis, average-re ected-power imaging allows for greater contrast between the image intensities of the strands versus thebackground noise, making it easier to localize the strands. This is also supported by visuallycomparing B-mode and average-re ected-power strand images from the experiment.Strands are di cult to localize in a traditional B-Mode image due to applied thresholds andcompressions that decrease the B-Mode image’s dynamic range. The reason for these compressionsis that B-Mode images are mainly used to delineate between tissues in the body which have verysimilar acoustic impedance factors. An example of this is the use of B-Mode imaging to delineatethe boundary of the prostate. The compressed dynamic range of the B-Mode image enhancesthe contrast between the relatively similar tissues of the prostate and the surrounding area. Interms of strand localization, the acoustic impedance factor of the strand is very di erent fromthe surrounding tissue. The full extent of this di erence can’t be captured by traditional B-Modeimaging. The compressed contrast range of this imaging mode means that extremely strongultrasound re ectors, like the strand, become saturated in B-Mode images, cutting short boththeir intensity and contrast.Average-re ected-power is computed over the full range of the raw RF data. This allows it tocapture the large contrast di erence between strands and the surrounding tissue. Strands becomemore visible and easier to localize as a result. The drawback of this increased range is that thesmaller contrast di erences between the di erent tissue types become harder to discern. Thislimits the average-re ected-power method to localizing implanted seeds, strand and other objectsthat give extremely high intensity responses.Strand Localization Looking at the sagittal image sweeps across the strand for di erentstrand orientation, both strand types give similar responses at parallel orientations. At theseorientations, both the EchoStrandTM and regular strand gives a tight, tall intensity peak thatfalls o signi cantly after 2 to 3 degrees from the peak intensity. The peak corresponds to wherethe image plane is incident to the strand. The intensity response of the strand also varies along426.1. Discussionsits length and this uncertainty is represented by the error bars of the image sweep plot. At theparallel orientations, the error in intensity is relative small compared to the actual intensity value.At strand orientations above six degrees, the EchoStrandTM is still able to maintain a rela-tively high peak intensity response, though the peak is not as tight. The relative errors in peakintensity have also increased. The peak intensities of the regular strand at these orientations arenow very low with extremely high error.In terms of localizing strands across di erent image planes, it is much easier to localize thosethat have a high peak intensity with a small degree of error than those that have a low peakintensity with a large amount of uncertainty.For example, based on the data in Figure 4.6, when attempting to determine if an EchoStrandTMat zero degree orientation is on or close to the current image plane, we look for an intensity re-sponse corresponding to a IOD value of 8x106 on a ROI along the strand. The image sweep plottells us that the strand response is only this high when the strand is very close to the image plane.Contrast this to localization conducted on a regular strand with an orientation of 10 degrees. Itis very hard to pick a intensity cut-o value in this case due to the short peak and the largeerror in the intensity values. Picking a value that account for the low end of the variation inpeak intensity will cause the strand to be detected across a large number of image planes. It istherefore extremely hard to localize the regular strand at non-parallel orientations.Intensity and CNR Both quantitative analysis and the phantom experiments show that bothstrand intensity and contrast to background decrease as the strands become less parallel. Intensitymeasurement on strand (Shown in Figure 4.6) in water shows a drop o of strand intensity between0 to 8 degree orientations. At 8 degrees and above, the strand intensities remain relativelyconstant. For all orientations, the response of the EchoStrandTM is higher than the regularstrand.Contrast to background noise (CNR) measurement (See Figure 5.5) indicates that the strand’scontrast to noise ratio decreases with non-parallel orientations. The contrast to background noisebetween the two strand types are similar at low angled orientations but the EchoStrandTM hasa much higher CNR at high orientations than the regular strand.Visual inspection of the B-Mode and RF images from both strands in water and strands inphantom supports the quantitative data. Both strands su er a rapid decay in intensity with non-parallel orientations but the rate of decay is greater for the regular strand. The regular strand’scontiguity also begins to break done at 8 degrees orientation and above resulting in large gapsappearing along the length of the strand.In the phantom experiment, both the regular strand and the EchoStrandTM are contrastedagainst the background at parallel strand orientations. However, due to the fact that the intensityof the regular strand is observed to decrease faster than the EchoStrandTM, the regular strandis no longer discernable at orientations above 15 degrees. The EchoStrandTM is still discernable436.1. Discussionsup till the 20 degree orientation.The higher intensity response and contrast to background noise of the EchoStrandsTM indicatethat it is a better candidate in strand localization. The most basic operation in segmenting thestrands of interest from background noise is to apply a intensity threshold to the ultrasoundimage. With a higher strand intensity response, a high intensity threshold can be applied to theultrasound image to segment out the strand allowing for more noise to be  ltered. This resultsin a cleaner image for subsequent strand detection algorithms.The better contiguity of the EchoStrandTM over regular strands at non-parallel orientationsalso gives it another advantage. The contiguous strand outline allows for segmentation methodsthat take the strand’s known shape into account. It is much easier to identify strands that appearas a solid line than ones that shows up in broken pieces. One of the major hurdles in localizationimplanted seeds is their small size [23]. Identifying a much larger, contiguous strand structurewill overcome this problem.Strand Materials The better intensity response and contiguity of the EchoStrandTM, par-ticularly at non-parallel orientations, may be attributed to the micro-bubbles embedded in thespacer material.In regular strands, the core of the spacer material has a uniform composition. This means thatthe acoustic boundaries are only at the surface of the spacer material. However, the surface ofthe spacer material is smooth and  at meaning that mostly specular ultrasound re ections occurat this boundary. Based on the principles of specular re ection, it is expected that the intensityresponse of the regular strand becomes weaker when the strand has a non-parallel orientation asmost of the echoes are directed away from the transducer.With the EchoStrandTM, the micro-bubbles within the spacer material create a set of internalre ective boundaries. These boundaries are formed by the change in acoustic impedance factorat the intersection between the spacer material and the gas inside the bubble. These sets ofboundaries are irregular due to the tiny size of the micro-bubbles and allow non-specular re ectionto occur. The echoes are scattered in all directions making the intensity response from thesebubbles independent of orientation. This is one plausible reason why EchoStrandTM gives abetter response than regular strand at non-parallel strand orientations.However, it is surprising that the presence of micro-bubbles does not signi cant improve theintensity of the EchoStrandsTM. These micro-bubbles have been observed in other experimentsto result in much higher intensity responses[1, 17].One explanation for low response is that the micro-bubbles are relatively few in numberwithin the EchoStrandTM material. Looking carefully at the strand, micro-bubbles are seenplaced lengthwise along the strand in a single, roughly uniform column. If the number of thesebubbles is to increase, a more intense response may result.In addition, non-specular re ection scatters the incoming ultrasound beam. Scattered ultra-446.2. Conclusionssound beams travel in many di erent directs with only a few that are actually received by thetransducer. This means that the non-specular responses generated by the micro-bubbles are muchless intense than the specular re ections generated by the surface of the strand.The reason why micro-bubbles are found to generate high intensity responses in other exper-iments is because those experiments use free- oating micro-bubbles. In those cases, the micro-bubbles have a very soft and  exible shell and is suspended in liquid. Incident ultrasound beamscause them to resonate in place. Their resonance then generates a series of intense ultrasoundechoes that shows up intensely when imaged. However, this resonance is hampered if the shell ofthe micro-bubble is rigid[1, 5].In the case of EchoStrandsTM, the strand material is extremely rigid and encases the entiremicro-bubble. This prevents any resonance from taking place. If the micro-bubbles within thestrand are allowed to  oat freely within the spacer material, then the intensity response is expectedto be much higher. However, this environment is be extremely hard to create and maintain.6.2 ConclusionsThis experiment shows that average-re ected-power imaging is successful in enhancing the con-trast of brachytherapy strands against a noisy background for both regular strands and EchoStrandsTMover a wide range of strand orientations.The ultrasound intensity response and contrast to noise ratio of both strand types decreaseat non-parallel strand orientations. However, the EchoStrandTM gives a slightly higher intensityresponse across all orientations than the regular strand and maintains better contiguity in bothB-Mode and average-re ected-power images. The EchoStrandTM is also found to give bettercontrast against background noise than regular strands especially at non-parallel orientations.The outcome of this experiment suggest that the used of both EchoStrandsTM and average-re ected-power imaging allows for better strand localization. Regular strands that aren’t visiblein traditional B-Mode due to noise or orientations can be successfully localized if replaced withEchoStrandsTM and imaged using average-re ected-power imaging.6.3 Future WorkThe promising results of this experiment indicate that detecting EchoStrandsTM with average-re ected-power imaging can be a valid technique in strand localization. Though the phantomused in this experiment roughly models the acoustic density of real tissue, it cannot simulate thewide range of calci cation and structural patterns found in them.A clinical experiment will have to be conducted to attempt to localize EchoStrandsTM usingthis technique on live patients. If the outcome of this clinical study proves fruitful, an intra-operative strand detection system can be designed to allow accurate strand localization and456.3. Future Workreal-time dosimetry to be incorporated into brachytherapy procedures.46Bibliography[1] F. Calliada, R. Campani, O. Bottinelli, A. Bozzini, and M. G. Sommaruga. Ultrasoundcontrast agents basic princicples. Eur. J. of Radiology, 27:S157{S160, 1998.[2] B. J. Davis, J. F. Greenleaf, and et al. Measurement of the ultrasound backscatter signalfrom three seed types as a function of incidence angle: Application to permanent prostatebrachytherapy. Int. J. Radiation Oncology Biol. Phys., 57(4):1174{1182, 2003.[3] D. French, J. Morris, M. Keyes, and S. Salcudean. Real-time dosimetry for prostate brachyt-hearpy using trus and  uoroscopy. MICCAI, pages 983{991, 2004.[4] P. Grimm and J. Sylvester. Advances in brachytherapy. Rev. Urol., 6(suppl 4):S37{S48,2004.[5] L. Ho , P. C. Sontum, and J. M. Hovem. Oscillations of polymeric microbubbles: E ect ofthe encapsulating shell. J. Acoustic Society of America, 107(4):2272{2280, 2000.[6] L. Marrett, P. De, D. Dryer, and et al. Canadian Cancer Society’s Steering Committee:Canadian Cancer Statistics 2009. Canadian Cancer Society, 2009.[7] H. Matzkin, I. Kaver, and et al. Comparison between two iodine-125 brachytherapy im-plant techniques: pre-planning and intra-operative by various dosimetry quality indicators.Radiotherapy and Oncology, 68:289{294, 2003.[8] S. A. McAleavey, D. J. Roubens, and K. J. Parker. Doppler ultrasound imaging of magneti-cally vibrated brachytherapy seeds. IEEE Transactions on Biomedical Engineering, 50:252{255, 2003.[9] F. G. Mitri, P. Trompette, and J. Y. Chapelon. Improving the use of vibro-acoustographyfor brachytherapy metal seed imaging: A feasibility study. IEEE Transactions in BiomedicalEngineering, 23:1{6, 2004.[10] W. J. Morris, M. Keyes, D. Palma, and et al. Population-based study of biochemical andsurvival outcomes after permanent 125i brachytherapy for low- and intermediate-risk prostatecancer. Oncology, 10:860{865, 2009.47Bibliography[11] S. Nag, D. Beyer, and et al. American brachytherapy society (abs) recommendations fortransperineal permanent brachytherapy of prostate cancer. Int. J. Radiation Oncology Biol.Phys., 44(4):789{799, 1999.[12] S. Nag, W. Bice, and et al. American brachytherapy society recommendations for permanentprostate brachytherapy postimplant dosimetric analysis. Int. J. Radiation Oncology Biol.Phys., 46(1):221{230, 2000.[13] S. Nag, J. P. Ciezki, and et al. Intraoperative planning and evaluation of permanent prostatebrachytherapy: Report of the american brachytherapy society. Int. J. Radiation OncologyBiol. Phys., 51(5):1422{1430, 2001.[14] A. V. Oppenheim. Digital Signal Processing. Prentice Hall, 1975.[15] A. Patriciu, D. Petrisor, and et al. Brachytherapy seed placement under mri guidance. IEEETransactions on Biomedical Engineering, 54:1499{1506, 2007.[16] M. S. Patterson and F. S. Foster. The improvement and quantitative assessment of b-modeimages produced by annular array/cone hybrid. Ultrasonic Imaging, 5:195{213, 1983.[17] E. Quaia. Microbubble ultrasound contrast agents: an update. Eur Radiol, 17:1995{2008,2007.[18] R. G. Stock, J. Kao, and N. N. Stone. Penile erectile function after permanent radioactiveseed implantation for treatment of prostate cancer. The Journal of Urol., 165:436{439, 2001.[19] R. G. Stock, N. N. Stone, M. Dahlal, and Y. C. Lo. What is the optimal dose for 125iprostate implants? a dose-response analysis of biochemical control ,posttreatment prostatebiopsies, and long-term urinary symptoms. Brachytherapy, 1:83{89, 2002.[20] R. G. Stock, N. N. Stone, A. Tabert, C. Iannuzzi, and J. K. DeWyngaert. A dose-responsestudy for i-125 prostate implants. Int. J. Radiation Oncology Biol. Phys., 41(1):101{108,1998.[21] N. M. Tole and H. Ostensen. Basic Physics of Ultrasonographic Imaging. World HealthOrganization, 2005.[22] K. Wallner, J. Roy, and L. Harrison. Dosimetry guidelines to minimize urethral and rectalmorbidity following transperineal i-125 prostate brachytherapy. Int. J. Radiation OncologyBiol. Phys., 32(2):465{471, 1995.[23] X.Wen, S. E. Salcudean, and P. D. Lawrence. Detection of brachytherapy seeds using ultra-sound radio frequency signals. Proc. of SPIE, 6147:1605{7422, 2006.48Bibliography[24] Y. Yu, Lowell L. Anderson, and et al. Permanent prostate seed implant brachytherapy:Report of the american association of physicists in medicine task group no. 64. Med. Phys.,26(10):2054{2073, 1999.[25] M. J. Zelefsky, Y. Yamada, and et al. Postimplantation dosimetric analysis of permanenttransperineal prostate implantation: Improved dose distributions with an intraoperativecomputer-optimized conformal planning technique. Int. J. Radiation Oncology Biol. Phys,48(2):601{608, 2000.49


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