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Purpose: Although quality assurance (QA) is crucial in radiation oncology departments, substantial efforts are required to monitor and ensure compliance to high standards. This work aims to analyze the impact of implementing a centralized and automated tracking dashboard on compliance and variance observed in radiation therapy QA results for linear accelerators., Methods and Materials: The study was performed in a large academic center with 7 linear accelerators. An in-house QA Dashboard was implemented in 2019 with design specifications including automated monitoring and visualization of QA progress, ease of use and accessibility, ease of integration, adaptability to new technologies, and facilitation of automated reminders. Monthly QA data were collected between 2016 and 2022 to analyze compliance pre- and post-dashboard implementation. Compliance was characterized as the percentage of tests completed on time. In addition, variance trends for linear accelerator dosimetry measurements and imaging were analyzed over 7 years., Results: In total, 76,066 records were analyzed. Of these records, 73,187 QA measurements were completed on time. Overall QA compliance increased from 75% in 2016 to >99% in 2019 after successful implementation of the QA Dashboard. The main improvement was observed for tests that were implemented more recently, eg, imaging QA and formal recording of daily QA review by physicists. The coefficient of variation was reduced by approximately a factor of 2 for imaging QA after the implementation of the QA Dashboard. For recorded dosimetry measurements, no substantial change in variance was observed., Conclusions: Implementation of the QA Dashboard resulted in a distinct increase in QA compliance. Reduction in the variance in QA measurements was observed for all imaging modalities. These findings demonstrate high impact of automated tracking QA tools on improved compliance and accuracy of QA., (© 2024 The Author(s).)

Interstitial and intracavitary gynecological HDR brachytherapy involve precise, localized delivery to targets with high dose gradients, sparing adjacent organs at risk (OAR). Due to the proximity of the rectum, bowel and bladder to the target, deviations in the applicator or catheter with respect to patient anatomy can significantly increase dose to OAR. The magnitude and direction of applicator and catheter migration at each fraction was assessed for template interstitial and tandem and ring (T&R) cohorts. The cohort included twelve gynecological patients with intact cervical lesions treated with external beam and brachytherapy. Pre-treatment CT images were registered to the simulation CT with respect to the target. Treatment catheter positions transformed into the planning CT coordinate system to evaluate localized catheter displacement and dose distributions calculated at each fraction. Dose was evaluated on the planning CT with planning contours and dwell locations at treatment position. Absolute deviation, depth and deflection angle for all patients were 4.6 ± 4.2 mm, -1.4 ± 4.0 mm, and 3.1 ± 2.3° respectively (n = 516 catheter positions for all treatment fractions and patients, mean ± SD). Absolute catheter deviation and deflection magnitude for interstitial treatments increased overall with each subsequent fraction with an overall increase of catheter retraction at each fraction (p < 0.005, n = 492 catheters, Kruskal-Wallis). A target EQD2 D90 reduction of 10 ± 10% and 7.7 ± 8.7% of the planned dose for interstitial and T&R cohorts respectively. There was an overall increase in bladder and rectal doses at each fraction. Catheter tracking in interstitial and intracavitary gynecological treatments with CT imaging revealed significant changes in catheter positioning with respect to the target volume. Overall deviations increased in magnitude with each subsequent fraction in the interstitial treatments. This caused patient dosimetry deviations, including target dose reduction and adjacent OAR doses changes., (Copyright © 2021 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

This paper describes a fast, wide-angle, afocal, catadioptric optical assembly designed and used for the projection of coherent collimated beams in Fourier-sampling computational microscopy, which demands an unorthodox set of optical requirements unmet by traditional imaging designs. The system accepts a diverging set of collimated beams as an input and produces a converging set of collimated beams that overlap on the surface of a target at 5 m scale distances. We derive equations for the focal surfaces relevant for system alignment and report the results of simulations of the optical performance of the system for axially symmetric and asymmetric beam interferometry. We also describe a method to vary the microscope imaging distance by up to one meter through small positional shifts in the optical elements.

The use of PARP inhibitors in combination with radiotherapy is a promising strategy to locally enhance DNA damage in tumors. Here we show that radiation-resistant cells and tumors derived from a Pten/Trp53 -deficient mouse model of advanced prostate cancer are rendered radiation sensitive following treatment with NanoOlaparib, a lipid-based injectable nanoformulation of olaparib. This enhancement in radiosensitivity is accompanied by radiation dose-dependent changes in γ-H2AX expression and is specific to NanoOlaparib alone. In animals, twice-weekly intravenous administration of NanoOlaparib results in significant tumor growth inhibition, whereas previous studies of oral olaparib as monotherapy have shown no therapeutic efficacy. When NanoOlaparib is administered prior to radiation, a single dose of radiation is sufficient to triple the median mouse survival time compared to radiation only controls. Half of mice treated with NanoOlaparib + radiation achieved a complete response over the 13-week study duration. Using ferumoxytol as a surrogate nanoparticle, MRI studies revealed that NanoOlaparib enhances the intratumoral accumulation of systemically administered nanoparticles. NanoOlaparib-treated tumors showed up to 19-fold higher nanoparticle accumulation compared to untreated and radiation-only controls, suggesting that the in vivo efficacy of NanoOlaparib may be potentiated by its ability to enhance its own accumulation. Together, these data suggest that NanoOlaparib may be a promising new strategy for enhancing the radiosensitivity of radiation-resistant tumors lacking BRCA mutations, such as those with PTEN and TP53 deletions. Mol Cancer Ther; 16(7); 1279-89. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Active magnetic resonance (MR) tracking for gynecologic brachytherapy was made possible by attaching the micro radiofrequency coils to the brachytherapy applicator. The rectangular planar micro coil was fabricated using flexible printed circuits with dimensions of 8mm×1.5mm. A 5-Fr (1.6mm) tungsten brachytherapy stylet was custom-machined to incorporate the micro coils. The finite element analysis and the phantom tissue studies show that the proposed device enables in situ , real-time guidance of access routes to the target anatomy safely and accurately. The setup was tested in a Siemens 3T MR scanner. The micro coils can be localized rapidly (up to 40 Hz) and precisely (resolution: 0.6×0.6×0.6mm 3 ) using an MR-tracking sequence.

An unstable patient presented with an enlarging splenic hematoma, for whom splenectomy was contraindicated. The decision was made to treat this patient with subtotal splenic embolization. Initial attempts at embolotherapy using a conventional end-hole catheter resulted in a false angiographic end point with reflux into short gastric arteries, likely due to splenic parenchymal pressurization from the hematoma. The Surefire antireflux device (Surefire Medical Inc, Westminster, Colo) was therefore employed. The Surefire device allowed successful subtotal splenic embolization. Whereas it is currently primarily used in hepatic interventional oncology, we have shown that it can be successfully used in other settings to increase embolization efficiency while mitigating nontargeted embolization., (© 2015 The Authors.)

We report a miniature, lightweight fiber-coupled confocal fluorescence microscope that incorporates an electrowetting variable focus lens to provide axial scanning for full three-dimensional (3D) imaging. Lateral scanning is accomplished by coupling our device to a laser-scanning confocal microscope through a coherent imaging fiber-bundle. The optical components of the device are combined in a custom 3D-printed adapter with an assembled weight of <2  g that can be mounted onto the head of a mouse. Confocal sectioning provides an axial resolution of ∼12  μm and an axial scan range of ∼80  μm. The lateral field-of-view is 300 μm, and the lateral resolution is 1.8 μm. We determined these parameters by imaging fixed sections of mouse neuronal tissue labeled with green fluorescent protein (GFP) and fluorescent bead samples in agarose gel. To demonstrate viability for imaging intact tissue, we resolved multiple optical sections of ex vivo mouse olfactory nerve fibers expressing yellow fluorescent protein (YFP).

Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits., Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues., Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days., Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The traditional role of radiology in the multidisciplinary approach to modern trauma care has been primarily diagnostic and noninvasive. With the advent of more sophisticated and faster imaging equipment, computed tomography has further entrenched its role as the workhorse of trauma imaging. However, the specialty has evolved over the years with various therapeutic techniques now part of the interventional radiology armamentarium. Several of these techniques have become essential for the management of critically ill trauma patients. This article provides an overview of the common imaging findings of vascular and solid organ trauma from head to toe and subsequent endovascular interventions in these critically ill trauma patients., (Copyright © 2014 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.)

Gynecologic malignancies, including cervical, endometrial, ovarian, vaginal and vulvar cancers, cause significant mortality in women worldwide. The standard care for many primary and recurrent gynecologic cancers consists of chemoradiation followed by brachytherapy. In high dose rate (HDR) brachytherapy, intracavitary applicators and/or interstitial needles are placed directly inside the cancerous tissue so as to provide catheters to deliver high doses of radiation. Although technology for the navigation of catheters and needles is well developed for procedures such as prostate biopsy, brain biopsy, and cardiac ablation, it is notably lacking for gynecologic HDR brachytherapy. Using a benchtop study that closely mimics the clinical interstitial gynecologic brachytherapy procedure, we developed a method for evaluating the accuracy of image-guided catheter placement. Future bedside translation of this technology offers the potential benefit of maximizing tumor coverage during catheter placement while avoiding damage to the adjacent organs, for example bladder, rectum and bowel. In the study, two independent experiments were performed on a phantom model to evaluate the targeting accuracy of an electromagnetic (EM) tracking system. The procedure was carried out using a laptop computer (2.1GHz Intel Core i7 computer, 8GB RAM, Windows 7 64-bit), an EM Aurora tracking system with a 1.3mm diameter 6 DOF sensor, and 6F (2 mm) brachytherapy catheters inserted through a Syed-Neblett applicator. The 3D Slicer and PLUS open source software were used to develop the system. The mean of the targeting error was less than 2.9mm, which is comparable to the targeting errors in commercial clinical navigation systems.

The advent of nanotechnology has bolstered a variety of nanoparticles based platforms for different biomedical applications. A better understanding for engineering novel nanoparticles for applications in cancer staging and therapy requires careful assessment of the nanoparticle's physico-chemical properties. Herein we report a facile synthesis method for PEGylated PLGA nanoparticles encapsulating anti-cancer drug doxorubicin for cancer imaging and therapy. The simple nanoprecipitation method reported here resulted in very robust PEGylated PLGA nanoparticles with close to 95% drug encapsulation efficiency. The nanoparticles showed a size of ~110 nm as characterized by TEM and DLS. The nanoparticles were further characterized by optical UV-Visible and fluorescence spectroscopy. The encapsulated doxorubicin showed a sustained release (>80%) from the nanoparticles matrix over a period of 8 days. The drug delivery efficiency of the nanoparticles was confirmed in vitro confocal imaging with PC3 and HeLa cell lines. In vitro quantitative estimation of drug accumulation in PC3 cell line showed a 22 times higher concentration of drug in case of nanoparticles based formulation in comparison to free drug and this was further reflected in the in vitro cytotoxicity assays. Overall the synthesis method reported here provides a simple and robust PLGA based platform for efficient drug delivery and imaging of cancer cells in vitro and in vivo.

Registration of pre- to intra-procedural prostate images needs to handle the large changes in position and shape of the prostate caused by varying rectal filling and patient positioning. We describe a probabilistic method for non-rigid registration of prostate images which can quantify the most probable deformation as well as the uncertainty of the estimated deformation. The method is based on a biomechanical Finite Element model which treats the prostate as an elastic material. We use a Markov Chain Monte Carlo sampler to draw deformation configurations from the posterior distribution. In practice, we simultaneously estimate the boundary conditions (surface displacements) and the internal deformations of our biomechanical model. The proposed method was validated on a clinical MRI dataset with registration results comparable to previously published methods, but with the added benefit of also providing uncertainty estimates which may be important to take into account during prostate biopsy and brachytherapy procedures.

Purpose: To characterize and evaluate chitosan film containing PLGA nanoparticles (NPs) as a platform for localized dual-drug release., Methods: Fluorescent Paclitaxel (FPTX), a hydrophobic drug, was incorporated into PLGA NPs. FPTX-loaded PLGA NPs and Carboxyfluorescein (CF), a hydrophilic model drug, were embedded into chitosan films. Release of CF and NPs from chitosan and release of FPTX from PLGA NPs were monitored by fluorescence. The stability of the platform was observed through SEM and dynamic light scattering (DLS)., Results: Chitosan films containing CF and FPTX-loaded PLGA NPs showed a biphasic release profile. In the first phase, 78% of CF and 34% of NPs were released within few days. In the second phase, the release was slower, showing an additional release of 22% of CF and 18% of NPs after 3 weeks. SEM images and DLS measurements showed that NP release depends on film degradation rate. FPTX-loaded PLGA NPs showed the release of 19.8% of total drug in 2 days, and no additional release was detected in the next 26 days., Conclusions: The ability of chitosan film containing PLGA NPs to coat gold surface and to incorporate and release two different drugs of different hydrophilicity make it a promising platform for localized dual-drug release.

Purpose: To evaluate factors affecting survival and toxicity in patients with stage IIIB cervical cancer treated with external-beam radiotherapy and low-dose-rate brachytherapy., Materials and Methods: Seventy patients with stage IIIB cervical cancer treated between 1980 and 2000 were identified. A total of 51 patients had a tandem placed; 19 had interstitial brachytherapy only with no tandem placed. Univariate and multivariate analyses assessed factors potentially associated with survival and long-term complications., Results: Kaplan-Meier estimates for overall survival (OS) for the entire population at 2, 3, and 4 years were 43%, 29%, and 27%, respectively. Overall survival differed significantly between those treated with a tandem versus those treated without (log rank P < 0.0001). Significant predictors of OS on univariate Cox regression were presence of a tandem (hazards ratio [HR], 0.31; P = 0.0001) and cumulative dose to point A (HR, 0.95; P = 0.0001). Multivariate regression showed that the presence of a tandem was the only significant predictor of OS (HR, 0.46; P = 0.04). There were no significant predictors of complications., Conclusions: The dose to point A of approximately 85 Gy as associated with tandem use was a significant predictor of survival in patients with stage IIIB cervical carcinoma, indicating the significance of the central location of the high dose provided by the tandem. Patients selected for interstitial brachytherapy alone must receive sufficient dose, and a tandem should be placed whenever feasible for all patients with an intact uterus treated for locally advanced cervical cancer.

We present a new dose delivery scheme utilizing sub-conformal dynamic arc (sub-CD-ARC) with a dynamic multileaf collimator (dMLC) modulation in a single rotation. In sub-conformal delivery, a MLC aperture conforms not to the whole target but to its portion, simultaneously completely avoiding organs at risk (OARs). In CD-ARC therapy, the dose deposition level depends on the target width and distance to the axis of rotation, and therefore the use of multiple arcs is necessary to achieve a uniform dose within the target in 3D. In our delivery scheme, the dose deposition variations symptomatic of non-modulating sub-CD-ARC are compensated for in 3D by a quasi-periodic monotonic dMLC modulation. For this reason, we call this scheme sub-conformal dynamic modulated arc (sub-CD-MARC) therapy. The advantage of using such a modulation is that MLC leaf motion has just a few control points, and that an inverse planning problem is reduced to a linear equation problem with a few unknown parameters, which have clear physical meaning. We show the general dosimetric properties of sub-CD-ARC and sub-CD-MARC for a specific geometry of the target and OARs (rotational symmetry with varying inner and outer radii along the axis of rotation). In addition, we present numerical results of sub-CD-MARC inverse planning optimization.

Purpose: To investigate motion and shape change when using an endorectal balloon (ERB) in patients receiving radiotherapy for prostate cancer., Methods: In nine patients treated for prostate cancer using an ERB, the anterior wall of the ERB was contoured on right lateral images taken immediately before irradiation, and on left lateral images taken immediately after irradiation. Changes in the contours were used to calculate inter-fraction shape change and inter-imaging motion and shape change. Inter-imaging motion describes changes that occur after the right lateral image is taken that are seen in the left lateral image., Results: Eighty-six percent of all inter-imaging shifts of the anterior wall of the ERB were in the posterior direction (mean: 1.8 mm, 1 SD: 1.8 mm, maximum posterior shift: 2.8-7.2 mm). The inter-fraction shape change (1 SD) of the anterior wall was equivalent to a change in the angle of the balloon of 2.5-5.7 degrees, with a range of 8-20 degrees, depending on the patient. Inter-imaging shape changes were similar in size., Conclusions: The inter-imaging motion and shape changes may be explained by the patient relaxing some time after insertion of the ERB, indicating that it could be reduced by a waiting period after insertion before irradiation. Development of image-guided localization strategies should consider intra-fraction motion and also inter- and intra-fraction shape change.

Results are presented comparing Monte Carlo (MC) calculations for dynamic IMRT treatments of tumors in the sinus region with Eclipse treatment planning system dose calculations, and ion chamber measurements. The EGS4nrc MC code, BEAMnrc, was commissioned to simulate a Varian 21Ex Linac for both open and IMRT fields. The accuracy of the simulation for IMRT plans was evaluated using a head phantom by comparing MC, Eclipse, TLD results, and ion chamber in solid water phantom measurements. The MC code was then used to simulate dose distributions for five patients who were treated using dynamic IMRT for tumors in the sinus region. The results were compared with absolute and relative dose distributions calculated using Eclipse (pencil beam, modified-Batho inhomogeneity correction). Absolute dose differences were also compared with ion chamber results. Comparison of the doses calculated on the head phantom using MC, compared with Eclipse, ion chamber, and TLD measurements showed differences of -3.9%, -1.4%, and -2.0%, respectively (MC is colder). Relative dose distributions for the patient plans calculated using MC agreed well with those calculated using Eclipse with respect to targets and critical organs, indicating the modified-Batho correction is adequate. Average agreement for mean absolute target doses between MC and Eclipse was -3.0 +/-; 2.3% (1 s.d.). Agreement between ion chamber and Eclipse for these patients was -2.2 +/- 1.9%, compared with 0.2 +/- 2.0% for all head and neck IMRT patients. When Eclipse doses were corrected based on ion chamber results, agreement between MC and Eclipse was -0.7 +/- 2.0%, indicating a small systematic uncertainty in the doses calculated using the treatment planning system for this subset of patients.

Purpose: To evaluate the feasibility and to describe the acute toxicity of a real-time intraoperative magnetic resonance (MR)-image guided interstitial approach to treating vaginal recurrence of endometrial cancer., Methods and Materials: From February 2004 to April 2005, 10 patients with recurrent endometrial cancer underwent MR-guided interstitial brachytherapy. Parameters evaluated included needle placement, dose-volume histograms (DVH), and complications., Results: Magnetic resonance-image guidance resulted in accurate needle placement. Tumor DVH values included median volume, 47 cc; V100, 89%; V150, 61%; V200, 38%; D90, 71 Gy; and D100, 60 Gy. DVH of organs at risk resulted in a median D2cc of external beam and brachytherapy dose (% of brachytherapy prescription): bladder, 75Gy(3) (88%); rectum, 70Gy(3) (87%); and sigmoid, 56Gy(3) (41%). All patients experienced either a Grade 1 or 2 acute toxicity related to the radiation; only 1 patient had Grade 3 toxicity. No toxicities were attributable to the use of MR guidance., Conclusions: Real-time MR guidance during the insertion of interstitial needles reduces the likelihood of an inadvertent insertion of the needles into the bladder and the rectum. Three-dimensional dosimetry allows estimation of the dose to organs at risk. Toxicities are limited.

This work looks at the feasibility of an online adaptive radiation therapy concept that would detect the daily position and shape of the patient, and would then correct the daily treatment to account for any changes compared with planning position. In particular, it looks at the possibility of developing algorithms to correct for large complicated shape change. For co-planar beams, the dose in an axial plane is approximately associated with the positions of a single multi-leaf collimator (MLC) pair. We start with a primary plan, and automatically generate several secondary plans with gantry angles offset by regular increments. MLC sequences for each plan are calculated keeping monitor units (MUs) and number of segments constant for a given beam (fluences are different). Bulk registration (3D) of planning and daily CT images gives global shifts. Slice-by-slice (2D) registration gives local shifts and rotations about the longitudinal axis for each axial slice. The daily MLC sequence is then created for each axial slice/MLC leaf pair combination, by taking the MLC positions from the pre-calculated plan with the nearest rotation, and shifting using a beam's-eye-view calculation to account for local linear shifts. A planning study was carried out using two head and neck region MR images of a healthy volunteer which were contoured to simulate a base-of-tongue treatment: one with the head straight (used to simulate the planning image) and the other with the head tilted to the left (the daily image). Head and neck treatment was chosen to evaluate this technique because of its challenging nature, with varying internal and external contours, and multiple degrees of freedom. Shape change was significant: on a slice-by-slice basis, local rotations in the daily image varied from 2 to 31 degrees, and local shifts ranged from -0.2 to 0.5 cm and -0.4 to 0.0 cm in right-left and posterior-anterior directions, respectively. The adapted treatment gave reasonable target coverage (100%, 90% and 80% of the base-of-tongue, left nodes and right nodes, respectively, receiving the daily prescription dose), and kept the daily cord dose below the limit used in the original plan (65%, equivalent to 46 Gy over 35 fractions). Most of the loss of coverage was due to one shoulder being raised more superior relative to the other shoulder compared with the plan. This type of skew-like motion is not accounted for by the proposed ART technique. In conclusion, this technique has potential to correct for fairly extreme daily changes in patient setup, but some control of the daily position would still be necessary. Importantly, it was possible to combine treatments from different plans (MLC sequences) to correct for position and shape change.

Objectives: To evaluate the risk of acute urinary retention (AUR) and sequelae after urethra-sparing magnetic resonance imaging (MRI)-guided prostate brachytherapy., Methods: Between 1997 and 2003, MRI-guided prostate brachytherapy was performed after external beam radiotherapy (n = 60) or as monotherapy (n = 188) following a diagnosis of low-risk prostate adenocarcinoma. The median prostate gland volume was 40 cm3 (range 16 to 184). Of the 248 patients, 88 (35%) had prostate gland volumes greater than 45 cm3. The median follow-up was 40 months., Results: Of the 248 patients, 18 (7%) developed AUR. Of the 248 patients, 2% (3 of 160), 6% (3 of 49), 28% (8 of 29), and 40% (4 of 10) of patients experienced AUR if the prostate gland volume was less than 45, 45 to 60, 60 to 90, or greater than 90 cm(3), respectively (P <0.0001). Retention requiring intermittent self-catheterization resolved in one half of the patients by 2 weeks and had resolved in all patients by 6 weeks. At 1, 3, and 6 months after implantation, 100%, 57%, and 29% of patients who experienced AUR, respectively, used Flomax (P <0.0001). The mean Flomax dose used decreased from 0.9 mg at 1 month to 0.53 mg at 1 year., Conclusions: AUR after urethral-sparing MRI-guided prostate brachytherapy is volume dependent and is self-limited despite very large prostate gland volumes.

Purpose: When >25% of the rectum is irradiated to > or = 70 Gy, the risk of developing Grade 2 or higher rectal complications is significantly increased. This study evaluates the impact on dose to the rectum from the use of an intrarectal (IR) balloon device, previously shown to immobilize the prostate gland and localize the rectum, in patients receiving dose escalated 3-dimentional (3D) conformal radiation therapy., Materials and Methods: From July 2001 through February 2003, 28 consecutive patients with prostate cancer underwent computerized tomography-based simulation with and without the IR balloon in place. Treatment planning was performed for three clinical paradigms in which the IR balloon was not used at all (0 Gy), used during the cone-down for 15 treatments (28.35 Gy), or used for the entire course of 40 treatments (75.6 Gy). The three plans were compared for differences in the percent of rectum receiving >70 Gy., Results: Dose volume histogram (DVH) analysis revealed that the median(range) of percent rectal volume exceeding 70 Gy was 25% (12.7-41.5%), 7.5% (0.9-19.5%), and 3.6% (0-8.7%) for patients in whom the IR balloon was used for 0, 15, and 40 treatments, respectively. The percent of rectum exceeding 70 Gy was significantly different for all treatment plan comparisons (P < 0.0001)., Conclusions: Grade 2 or higher rectal toxicity may be minimized during dose escalated 3D conformal radiation therapy through the use of an IR balloon during the 3-week cone down portion of an 8-week treatment course., (Copyright 2004 Elsevier Inc.)

Purpose: The preplanned technique used for permanent prostate brachytherapy has limitations that may be overcome by intraoperative planning. The goal of the American Brachytherapy Society (ABS) project was to assess the current intraoperative planning process and explore the potential for improvement in intraoperative treatment planning (ITP)., Methods and Materials: Members of the ABS with expertise in ITP performed a literature review, reviewed their clinical experience with ITP, and explored the potential for improving the technique., Results: The ABS proposes the following terminology in regard to prostate planning process: *Preplanning--Creation of a plan a few days or weeks before the implant procedure. *Intraoperative planning--Treatment planning in the operating room (OR): the patient and transrectal ultrasound probe are not moved between the volume study and the seed insertion procedure. * Intraoperative preplanning--Creation of a plan in the OR just before the implant procedure, with immediate execution of the plan. *Interactive planning--Stepwise refinement of the treatment plan using computerized dose calculations derived from image-based needle position feedback. *Dynamic dose calculation--Constant updating of dose distribution calculations using continuous deposited seed position feedback. Both intraoperative preplanning and interactive planning are currently feasible and commercially available and may help to overcome many of the limitations of the preplanning technique. Dosimetric feedback based on imaged needle positions can be used to modify the ITP. However, the dynamic changes in prostate size and shape and in seed position that occur during the implant are not yet quantifiable with current technology, and ITP does not obviate the need for postimplant dosimetric analysis. The major current limitation of ITP is the inability to localize the seeds in relation to the prostate. Dynamic dose calculation can become a reality once these issues are solved. Future advances can be expected in methods of enhancing seed identification, in imaging techniques, and in the development of better source delivery systems. Additionally, ITP should be correlated with outcome studies, using dosimetric, toxicity, and efficacy endpoints., Conclusion: ITP addresses many of the limitations of current permanent prostate brachytherapy and has some advantages over the preplanned technique. Further technologic advancement will be needed to achieve dynamic real-time calculation of dose distribution from implanted sources, with constant updating to allow modification of subsequent seed placement and consistent, ideal dose distribution within the target volume.

Purpose: We report the findings of a transperineal magnetic resonance image (MRI) guided biopsy of the prostate in a man with increasing prostate specific antigen who was not a candidate for a transrectal ultrasound guided biopsy., Materials and Methods: Using an open configuration 0.5 Tesla MRI scanner and pelvic coil, a random sextant sample was obtained under real time MRI guidance from the peripheral zone of the prostate gland as well as a single core from each MRI defined lesion. The patient had previously undergone proctocolectomy for ulcerative colitis and, therefore, was not a candidate for transrectal ultrasound guided biopsy. Prior attempts to make the diagnosis of prostate cancer using a transurethral approach were unsuccessful., Results: The random sextant samples contained benign prostatic hyperplasia, whereas Gleason grade 3 + 3 = 6 adenocarcinoma was confirmed in 15% and 25% of the 2 cores obtained from the MRI targeted specimens of 2 defined lesions. The procedure was well tolerated by the patient., Conclusions: Transperineal MRI guided biopsy is a new technique that may be useful in detecting prostate cancer in men with increasing prostate specific antigen who are not candidates for transrectal ultrasound guided biopsy.

Purpose: Larger prostate gland volumes have been associated with long-term urinary morbidity in prostate interstitial radiation therapy utilizing ultrasound image guidance technique. This study was performed to identify the clinical and technical predictors of acute urinary retention following magnetic-resonance (MR)-guided prostate interstitial brachytherapy., Methods and Materials: Fifty patients underwent MR-guided prostate brachytherapy between December 1997 and March 1999. Patient selection was limited to men with stage T1cNXM0 disease, PSA of less than10 ng/mL, biopsy Gleason score not more than 3 + 4, and endorectal coil MR stage T2 disease. Dosimetry plans were developed in the operating room and (125)Iodine sources were implanted using MR real-time guidance. The peripheral zone (PZ) of the prostate gland was defined as the clinical target volume (CTV) and the minimum prescribed dose to the CTV was 137 Gy. The volumes of the PZ, transition zone (TZ), and total prostate gland volume were also determined by MR. Individual source strength ranged from 0.35 to 0.54 microGym(2)/h (NIST 99, median 0.46 microGym(2)/h) and the total implanted activity ranged from 17.0 to 43.1 mCi (median, 28.1 mCi) using 43-120 seeds (median, 79). The seeds were placed using MR-compatible biopsy needles (14-28, median, 19)., Results: The ability of clinical (MR defined prostate, PZ, and TZ volumes) and technical (number of catheters, number of seeds implanted, and total activity) factors to predict AUR for 50 men undergoing MR-guided prostate interstitial brachytherapy were evaluated using univariable and logistic regression multivariable analyses. Six men (12%) experienced AUR within 24 h after removal of the Foley catheter subsequent to prostate brachytherapy. The total number of seeds (p = 0.05), MR determined prostate volume (p < 0.01), and the MR-determined TZ volume (p < 0.01) were significant predictors of AUR on univariable analysis. Utilizing a multivariable logistic regression analysis, the TZ volume was the only significant predictor of AUR (p < 0.01). The prostate volume is highly correlated to the TZ volume (Spearman correlation coefficient of 0. 91) and was thus significant in the univariable analysis; however, the prostate volume did not add prognostic value in multivariable analysis., Conclusion: Benign prostatic hyperplasia (BPH) resulting in an enlarged TZ volume, is the most important predictor of AUR following MR-guided prostate interstitial radiation therapy. Although AUR was significant (60%) in men with moderate BPH (TZ volume >/= 50 cc), it was also self-limiting.

Purpose: A large number of men are diagnosed with early-stage prostate cancer as a result of prostate-specific antigen (PSA) screening. For many of these men, prostatectomy results in long-term freedom from biochemical and clinical failure. Despite limited follow-up data, ultrasound-guided prostate brachytherapy has gained acceptance as a treatment for early-stage prostate cancer, in part due to its favorable side effect profile and brief recovery period. We report on the use of three-dimensional real-time magnetic resonance (MR) guidance, which has several advantages compared with biplanar ultrasound guidance for prostate brachytherapy, including enhanced geometric and dosimetric feedback during the procedure., Materials and Methods: Median clinical target volume coverage of 96% was achieved using MR guidance. The ability to define more precisely the clinical target volume with MR and the use of real-time assessment of dose distribution resulted in an excellent acute side effect profile. Only 19% of patients required oral alpha1 blockers for postimplant urethritis and 9% required temporary reinsertion of the Foley catheter due to acute urinary obstruction., Conclusions: These results compare favorably to those of ultrasound-guided brachytherapy. Further follow-up is needed to ascertain the impact this technique will have on cancer control and long-term quality of life.

Background and Purpose: A real-time three-dimensional magnetic resonance imaging (MRI)-guided implant technique has been designed and implemented. This report summarizes the dosimetry achieved and the acute morbidity in the first patients., Patients and Methods: To date, 43 patients with clinical stage T(1c)N(X)M(0) prostate cancer, serum prostate specific antigen <10 ng/mL, and biopsy Gleason score no higher than 3 + 4 have been treated. The procedure was performed using an open magnet, with axial T1-weighted and fast spin echo images. The prescribed minimum radiation dose to the peripheral zone was 160 Gy. The total activity implanted ranged from 18.8 to 47.5 mCi using 43 to 120 (median 80) (125)I seeds. Dosimetric analyses were performed intraoperatively in real time for the tumor, anterior rectal wall, and prostatic urethra., Results: The percent of the clinical target volume receiving the prescription dose was 89% to 99% (median 96%). Using a conservative estimate of 164 Gy, no more than 9% of the urethral volume exceeded the tolerated dose. Using an estimated tolerated dose of 82 Gy, 30% to 100% (median 68%) of the anterior rectal wall volume was within the dose limit. Thirty-nine patients voided spontaneously within 3 hours of Foley catheter discontinuation, although four patients required recatheterization for a period. No patient reported gastrointestinal or sexual dysfunction during the first postoperative month., Conclusion: A real-time MR-guided technique can achieve a minimum of 89% coverage of the tumor volume while maintaining the prostatic urethra and most of the anterior rectal wall below tolerance levels. Acute morbidity was minimal. Further follow-up is needed to ascertain the impact on cancer control and quality of life.

Purpose: This study was performed to establish the dose-localization capability and acute toxicity of a real-time intraoperative magnetic resonance (MR) image-guided approach to prostate brachytherapy in select patients with clinically localized prostate cancer., Methods and Materials: Nine patients with 1997 American Joint Commission on Cancer (AJCC) clinical stage T1cNxM0 prostate cancer, prostate-specific antigen (PSA) < 10 ng/ml, biopsy Gleason score not exceeding 3 + 4, and endorectal coil MR stage T2 disease were enrolled into this study. The prescribed minimum peripheral dose was 160 Gy to the clinical target volume (CTV), which was the MR-defined peripheral zone (PZ) of the prostate gland. Using a real-time 0.5 Tesla intraoperative MR imaging unit, 5-mm image planes were obtained throughout the prostate gland. The PZ of the prostate gland, anterior rectal wall, and prostatic urethra were identified on the T2 weighted axial images by an MR radiologist. An optimized treatment plan for catheter insertion was generated intraoperatively. Each catheter containing the 125Iodine sources was placed under real-time MR guidance to ensure that its position in the coronal, sagittal, and axial planes was in agreement with the planned trajectory. Real-time dose- volume histogram analyses were used intraoperatively to optimize the dosimetry., Results: For the 9 study patients, 89-99% (median 94%) of the CTV received a minimum peripheral dose of 160 Gy and > or = 95% of the volume of the prostatic urethra and 42-89% (median 70%) of the volume of the anterior rectal wall received doses that were below the reported tolerance. All patients voided spontaneously within 3 h after discontinuation of the Foley catheter and no patient required more than a limited course (< or = 3 weeks) of oral alpha-1 blockers for postimplant urethritis., Conclusions: Real-time MR-guided interstitial radiation therapy provided the ability to achieve the planned optimized dose-volume histogram profiles to the CTV and healthy juxtaposed structures intraoperatively, with minimal acute morbidity.

Although data on the prevalence of injection drug use are an essential prerequisite for estimating the number of individuals infected with the human immunodeficiency virus (HIV), there have been few attempts to utilize statistical methods of population estimation based on multiple data sources. Data on 3,670 cases (2,866 individuals) were obtained from the HIV test register, drug treatment agencies, police records, and needle and syringe exchanges in Glasgow, Scotland, in 1990. Log-linear analysis was used to model the number of individuals in each of the sources. The model incorporating dependency among the three health care agencies (HIV test, drug treatment, and needle exchange) and independence of the police sample fitted the data well, with a residual chi 2 value of 2.9 (6 df). The expected value of the missing cell corresponding to absence from all four samples was 5,628, yielding an overall estimate of 8,494 injectors (95% confidence interval (CI) 7,491-9,721), for a prevalence rate of 1.35% for people aged 15-55 years in Glasgow during 1990. The high ratio of known to unknown injectors (1:2) resulted from the extensive coverage of known injectors and the relatively high level of overlap between the combined health care agency sample and the police sample. While further analysis demonstrated that the probability of appearing in the four samples varied by age and sex, heterogeneity in the population did not affect the choice of model or substantially alter the estimates for the total number of unknown injectors. A concurrent study of a community-wide sample of 503 injectors resulted in an HIV prevalence rate of 1.1% (95% CI 0.4-2.5%). The results of these studies were combined to produce a further estimate of 93 HIV-infected current injectors in Glasgow (95% CI 33-214).

An object moving against a textured background is accurately perceived when viewed foveally, but when viewed peripherally the object's perceived direction of motion may deviate from veridical by as much as 90 deg. The illusory direction is oblique to the orientation of the background contours, which may themselves be moving or stationary. In several experiments, we examined the boundary conditions for occurrence of the illusion and tested hypotheses concerning its basis. This illusion of perceived direction dramatizes differences in motion processing between the fovea and the periphery.

1. Human cells (HeLa) were cultured for periods up to 48 h in growth medium in the absence or presence of a range of concentrations of cardiac glycosides. In some experiments the potassium concentration of the medium was varied between 0.3 mM and the usual 5 mM. 2. For periods up to 2 h in ouabain the association and dissociation rate constants were measured and the equilibrium binding constant (KD) calculated; the apparent equilibrium binding constant (K'D) was measured after 1-2 days growth in ouabain. 3. Ouabain had a K'D after 2 days of 2-6 nM in 5 mM K+ growth medium, a 4 fold greater blocking effect on sodium pumps after 2 days than expected from the association and dissociation rate constants measured in untreated or previously ouabain-treated cells. 4. This effect was: (a) approximately the same over a range of external potassium concentrations from 0.3 to 5 mM, although the absolute effect of ouabain over this range of potassium was much different; (b) probably not due to different isoforms of pumps in cells grown in ouabain compared to untreated cells; (c) apparently not a consequence of internalisation of pump-glycoside complexes. 5. We conclude that ouabain has only a limited access to sodium pumps in whole cells; this could be because sodium pumps cycle continuously through an inaccessible region of the plasma membrane. This effect needs to be considered both in the assessment of the magnitude of the long term effects of cardiac glycosides on cells, and in the measurement of the glycoside affinities of various isoforms of the pump.