Histology to 3D in vivo MR registration for volumetric evaluation of MRgFUS treatment assessment biomarkers.

Advances in imaging and early cancer detection have increased interest in magnetic resonance (MR) guided focused ultrasound (MRgFUS) technologies for cancer treatment. MRgFUS ablation treatments could reduce surgical risks, preserve organ tissue and function, and improve patient quality of life. However, surgical resection and histological analysis remain the gold standard to assess cancer treatment response. For non-invasive ablation therapies such as MRgFUS, the treatment response must be determined through MR imaging biomarkers. However, current MR biomarkers are inconclusive and have not been rigorously evaluated against histology via accurate registration. Existing registration methods rely on anatomical features to directly register in vivo MR and histology. For MRgFUS applications in anatomies such as liver, kidney, or breast, anatomical features that are not caused by the treatment are often insufficient to drive direct registration. We present a novel MR to histology registration workflow that utilizes intermediate imaging and does not rely on anatomical MR features being visible in histology. The presented workflow yields an overall registration accuracy of 1.00 ± 0.13 mm. The developed registration pipeline is used to evaluate a common MRgFUS treatment assessment biomarker against histology. Evaluating MR biomarkers against histology using this registration pipeline will facilitate validating novel MRgFUS biomarkers to improve treatment assessment without surgical intervention. While the presented registration technique has been evaluated in a MRgFUS ablation treatment model, this technique could be potentially applied in any tissue to evaluate a variety of therapeutic options.

Cost-effectiveness of multiparametric magnetic resonance imaging and MRI-guided biopsy in a population-based prostate cancer screening setting using a micro-simulation model.

BACKGROUND: The introduction of multiparametric magnetic resonance imaging (mpMRI) and MRI-guided biopsy has improved the diagnosis of prostate cancer. However, it remains uncertain whether it is cost-effective, especially in a population-based screening strategy. METHODS: We used a micro-simulation model to assess the cost-effectiveness of an MRI-based prostate cancer screening in comparison to the classical prostate-specific antigen (PSA) screening, at a population level. The test sensitivity parameters for the mpMRI and MRI-guided biopsy, grade misclassification rates, utility estimates, and the unit costs of different interventions were obtained from literature. We assumed the same screening attendance rate and biopsy compliance rate for both strategies. A probabilistic sensitivity analysis, consisting of 1000 model runs, was performed to estimate a mean incremental cost-effectiveness ratio (ICER) and assess uncertainty. A €20,000 willingness-to-pay (WTP) threshold per quality-adjusted life year (QALY) gained, and a discounting rate of 3.5% was considered in the analysis. RESULTS: The MRI-based screening improved the life-years (LY) and QALYs gained by 3.5 and 3, respectively, in comparison to the classical screening pathway. Based on the probabilistic sensitivity analyses, the MRI screening pathway leads to total discounted mean incremental costs of €15,413 (95% confidence interval (CI) of €14,556-€16,272) compared to the classical screening pathway. The corresponding discounted mean incremental QALYs gained was 1.36 (95% CI of 1.31-1.40), resulting in a mean ICER of €11,355 per QALY gained. At a WTP threshold of €20,000, the MRI screening pathway has about 84% chance to be more cost-effective than the classical screening pathway. CONCLUSIONS: For triennial screening from age 55-64, incorporation of mpMRI as a reflex test after a positive PSA test result with a subsequent MRI-guided biopsy has a high probability to be more cost-effective as compared with the classical prostate cancer screening pathway.

Cost-effectiveness analysis of magnetic resonance-guided focused ultrasound ablation for palliation of refractory painful bone metastases.

OBJECTIVE: The aim of this study was to determine if magnetic resonance-guided focused ultrasound (MRgFUS) is cost-effective compared with medication, for refractory pain from bone metastases in the United States. METHODS: We constructed a Markov state transition model using TreeAge Pro software (TreeAge Software, Inc., Williamstown, MA, USA) to model costs, outcomes, and the cost-effectiveness of a treatment strategy using MRgFUS for palliative treatment of painful bone metastases compared with a Medication Only strategy (Figure 1). Model transition state probabilities, costs (in 2018 US$), and effectiveness data (quality-adjusted life-years [QALYs]) were derived from available literature, local expert opinion, and reimbursement patterns at two U.S. tertiary academic medical centers actively performing MRgFUS. Costs and QALYs, discounted at three percent per year, were accumulated each month over a 24-month time horizon. One-way and probabilistic sensitivity analyses were performed. RESULTS: In the base-case analysis, the MRgFUS treatment strategy costs an additional $11,863 over the 2-year time horizon to accumulate additional 0.22 QALYs, equal to a $54,160/QALY ICER, thus making MRgFUS the preferred strategy. One-way sensitivity analyses demonstrate that for the base-case analysis, the crossover point at which Medication Only would instead become the preferred strategy is $23,341 per treatment. Probabilistic sensitivity analyses demonstrate that 67 percent of model iterations supported the conclusion of the base case. CONCLUSIONS: Our model demonstrates that MRgFUS is cost-effective compared with Medication Only for palliation of painful bone metastases for patients with medically refractory metastatic bone pain across a range of sensitivity analyses.

Toxicity reduction required for MRI-guided radiotherapy to be cost-effective in the treatment of localized prostate cancer.

OBJECTIVE: To determine the toxicity reduction required to justify the added costs of MRI-guided radiotherapy (MR-IGRT) over CT-based image guided radiotherapy (CT-IGRT) for the treatment of localized prostate cancer. METHODS: The costs of delivering prostate cancer radiotherapy with MR-IGRT and CT-IGRT in conventional 39 fractions and stereotactic body radiotherapy (SBRT) 5 fractions schedules were determined using literature values and cost accounting from two institutions. Gastrointestinal and genitourinary toxicity rates associated with CT-IGRT were summarized from 20 studies. Toxicity-related costs and utilities were obtained from literature values and cost databases. Markov modeling was used to determine the savings per patient for every 1% relative reduction in acute and chronic toxicities by MR-IGRT over 15 years. The costs and quality adjusted life years (QALYs) saved with toxicity reduction were juxtaposed with the cost increase of MR-IGRT to determine toxicity reduction thresholds for cost-effectiveness. One way sensitivity analyses were performed. Standard $100,000 and $50,000 per QALY ratios were used. RESULTS: The added cost of MR-IGRT was $1,459 per course of SBRT and $10,129 per course of conventionally fractionated radiotherapy. Relative toxicity reductions of 7 and 14% are required for SBRT to be cost-effective using $100,000 and $50,000 per QALY, respectively. Conventional radiotherapy requires relative toxicity reductions of 50 and 94% to be cost-effective. CONCLUSION: From a healthcare perspective, MR-IGRT can reasonably be expected to be cost-effective. Hypofractionated schedules, such a five fraction SBRT, are most likely to be cost-effective as they require only slight reductions in toxicity (7-14%). ADVANCES IN KNOWLEDGE: This is the first detailed economic assessment of MR-IGRT, and it suggests that MR-IGRT can be cost-effective for prostate cancer treatment through toxicity reduction alone.

Prostate Cancer Detection Rate of Freehand versus 3-Dimensional Template Mapping Biopsy Using a Magnetic Resonance Imaging-Ultrasound Fusion Device in Biopsy Naïve Men.

PURPOSE: Targeted prostate biopsy devices include a 3-dimensional digital template grid to guide systematic biopsy locations. Following a template could better ensure uniform and well distributed sampling of the prostate compared to the traditional freehand biopsy approach, possibly decreasing the chance of false-negative biopsy. Thus, we determined cancer detection rates obtained by conventional freehand systematic sampling vs template mapping sampling using a magnetic resonance imaging-ultrasound fusion device. MATERIALS AND METHODS: Men who underwent first line conventional or image guided prostate biopsy were identified retrospectively in an institutional review board approved protocol. Excluded from study were men with prior biopsy or treatment or fewer than 10 cores taken. Targeted cores obtained by image guided biopsy were censored from analysis to simulate systematic template biopsy. The resulting cancer detection rate was compared to that of conventional biopsy. RESULTS: We identified 1,582 patients between 2006 and 2014 who met the criteria for analysis, including 1,052 who underwent conventional biopsy and 530 who underwent template biopsy with a magnetic resonance imaging-ultrasound fusion device. Patient age, prostate specific antigen and the number of systematic cores were the same in the 2 groups. Template biopsy detected any prostate cancer in 257 of 530 men (48.5%) and clinically significant cancer in 196 (37.0%) while conventional biopsy detected any cancer in 432 of 1,052 (41.0%) (p=0.005) and clinically significant cancer in 308 (29.2%) (p=0.002). CONCLUSIONS: Template mapping systematic biopsy detected more prostate cancer than conventional sampling in biopsy naïve men. It is a promising cost-effective alternative to magnetic resonance imaging-ultrasound fusion biopsy as an upfront screening tool.

The Association of Urologic Oncology Fellowship Training and Diagnostic Yield of Prostate Biopsy.

OBJECTIVE: To determine the relationship between urologic oncology fellowship training (UOFT) and diagnostic yield of prostate biopsy. METHODS: Retrospective review was conducted of patients who underwent prostate biopsy across the Cleveland Clinic between 2000 and 2018. Biopsies done by urologists with and without UOFT were detailed via descriptive statistics and appropriate (chi-square, Student t, Wilcoxon rank-sum) tests. Multivariate logistic regression was used to examine the association between UOFT and positive prostate biopsy, adjusting for relevant covariates. RESULTS: A total of 11,241 biopsies by 129 urologists had complete information available for review. Sixteen urologists (12.4%) had UOFT; 113 either completed a different fellowship or no fellowship. Those with UOFT were more likely to use MRI-guided biopsy (7.80% vs 3.05%, P <.0001), more likely to get a positive biopsy (41.25% vs 32.72%, P <.0001), and more likely to obtain an adequate number (by ≥12) of cores (90.25% vs 74.53%, P <.0001). UOFT remained a significant predictor of positivity when adjusting for patient age and race, PSA, 5-alpha-reductase-inhibitor use, year of biopsy, years in practice, and type of biopsy (MRI or transrectal ultrasound guided). UOFT also predicted higher-risk biopsy (Gleason sum ≥7), adjusting for the same variables, though this association lost significance when adjusting for adequacy of biopsy. The learning curve to achieve a higher percentage of positive biopsies was steeper for nonurologic oncology fellowship trained than for UOFT urologists. CONCLUSION: UOFT is associated with higher diagnostic yield on prostate biopsy, higher uptake of MRI-guided biopsy, and less steep learning curve. This may be due to patient selection, technique, or, as we demonstrate here, adherence to guidelines.

Early economic evaluation of MRI-guided laser interstitial thermal therapy (MRgLITT) and epilepsy surgery for mesial temporal lobe epilepsy.

BACKGROUND: MRI-guided laser interstitial thermal therapy (MRgLITT) is a new minimally invasive treatment for temporal lobe epilepsy (TLE), with limited effectiveness data. It is unknown if the cost savings associated with shorter hospitalization could offset the high equipment cost of MRgLITT. We examined the cost-utility of MRgLITT versus surgery for TLE from healthcare payer perspective, and the value of additional research to inform policy decision on MRgLITT. METHODS: We developed a microsimulation model to evaluate quality adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) of MRgLITT versus surgery in TLE, assuming life-time horizon and 1.5% discount rate. Model inputs were derived from the literature. We conducted threshold and sensitivity analyses to examine parameter uncertainties, and expected value of partial perfect information analyses to evaluate the expected monetary benefit of eliminating uncertainty on probabilities associated with MRgLITT. RESULTS: MRgLITT yielded 0.08 more QALYs and cost $7,821 higher than surgery, with ICER of $94,350/QALY. Influential parameters that could change model outcomes include probabilities of becoming seizure-free from disabling seizures state and returning to disabling seizures from seizure-free state 5 years after surgery and MRgLITT, cost of MRgLITT disposable equipment, and utilities of disabling seizures and seizure-free states of surgery and MRgLITT. The cost-effectiveness acceptability curve showed surgery was preferred in more than 50% of iterations. The expected monetary benefit of eliminating uncertainty for probabilities associated with MRgLITT was higher than for utilities associated with MRgLITT. CONCLUSIONS: MRgLITT resulted in more QALYs gained and higher costs compared to surgery in the base-case. The model was sensitive to variations in the cost of MRgLITT disposable equipment. There is value in conducting more research to reduce uncertainty on the probabilities and utilities of MRgLITT, but priority should be given to research focusing on improving the precision of estimates on effectiveness of MRgLITT.

Assessment of MR imaging during one-lung flooding in a large animal model.

OBJECTIVE: Magnetic resonance imaging (MRI) of the lung remains challenging due to the low tissue density, susceptibility artefacts, unfavourable relaxation times and motion. Previously, we demonstrated in vivo that one-lung flooding (OLF) with saline is a viable and safe approach. This study investigates the feasibility of OLF in an MRI environment and evaluates the flooding process on MR images. METHODS: OLF of the left lung was performed on five animals using a porcine model. Before, during and after OLF, standard T2w and T1w spin-echo (SE) and gradient-echo (GRE) sequences were applied at 3 T. RESULTS: The procedure was successfully performed in all animals. On T1w MRI, the flooded lung appeared homogenous and isointense with muscle tissue. On T2w images, vascular structures were highly hypointense, while the bronchi were clearly demarcated with hypointense wall and hyperintense lumen. The anatomical demarcation of the flooded lung from the surrounding organs was superior on T2w images. No outflow effects were seen, and no respiration triggering was required. DISCUSSION: OLF can be safely performed in an MR scanner with highly detailed visualization of the pulmonary structures on T2w images. The method provides new approaches to MRI-based image-guided pulmonary interventions using the presented experimental model.

Evaluation of a real-time magnetic resonance imaging-guided electrophysiology system for structural and electrophysiological ventricular tachycardia substrate assessment.

AIMS: Potential advantages of real-time magnetic resonance imaging (MRI)-guided electrophysiology (MR-EP) include contemporaneous three-dimensional substrate assessment at the time of intervention, improved procedural guidance, and ablation lesion assessment. We evaluated a novel real-time MR-EP system to perform endocardial voltage mapping and assessment of delayed conduction in a porcine ischaemia-reperfusion model. METHODS AND RESULTS: Sites of low voltage and slow conduction identified using the system were registered and compared to regions of late gadolinium enhancement (LGE) on MRI. The Sorensen-Dice similarity coefficient (DSC) between LGE scar maps and voltage maps was computed on a nodal basis. A total of 445 electrograms were recorded in sinus rhythm (range: 30-186) using the MR-EP system including 138 electrograms from LGE regions. Pacing captured at 103 sites; 47 (45.6%) sites had a stimulus-to-QRS (S-QRS) delay of ≥40 ms. Using conventional (0.5-1.5 mV) bipolar voltage thresholds, the sensitivity and specificity of voltage mapping using the MR-EP system to identify MR-derived LGE was 57% and 96%, respectively. Voltage mapping had a better predictive ability in detecting LGE compared to S-QRS measurements using this system (area under curve: 0.907 vs. 0.840). Using an electrical threshold of 1.5 mV to define abnormal myocardium, the total DSC, scar DSC, and normal myocardium DSC between voltage maps and LGE scar maps was 79.0 ± 6.0%, 35.0 ± 10.1%, and 90.4 ± 8.6%, respectively. CONCLUSION: Low-voltage zones and regions of delayed conduction determined using a real-time MR-EP system are moderately associated with LGE areas identified on MRI.

Real-time magnetic resonance imaging-guided cryoablation of the pulmonary veins with acute freeze-zone and chronic lesion assessment.

AIMS: The goals of this study were to develop a method that combines cryoablation with real-time magnetic resonance imaging (MRI) guidance for pulmonary vein isolation (PVI) and to further quantify the lesion formation by imaging both acute and chronic cryolesions. METHODS AND RESULTS: Investigational MRI-compatible cryoablation devices were created by modifying cryoballoons and cryocatheters. These devices were used in canines (n = 8) and a complete series of lesions (PVI: n = 5, superior vena cava: n = 4, focal: n = 13) were made under real-time MRI guidance. Late gadolinium enhancement (LGE) magnetic resonance imaging was acquired at acute and chronic time points. Late gadolinium enhancement magnetic resonance imagings show a significant amount of acute tissue injury immediately following cryoablation which subsides over time. In the pulmonary veins, scar covered 100% of the perimeter of the ostium of the veins acutely, which subsided to 95.6 ± 4.3% after 3 months. Focal point lesions showed significantly larger acute enhancement volumes compared to the volumes estimated from gross pathology measurements (0.4392 ± 0.28 cm3 vs. 0.1657 ± 0.08 cm3, P = 0.0043). Additionally, our results with focal point ablations indicate that freeze-zone formation reached a maximum area after 120 s. CONCLUSION: This study reports on the development of an MRI-based cryoablation system and shows that with acute cryolesions there is a large area of reversible injury. Real-time MRI provides the ability to visualize the freeze-zone formation during the freeze cycle and for focal lesions reaches a maximum after 120 s suggesting that for maximizing lesion size 120 s might be the lower limit for dosing duration.

Impact of multiparametric MRI and MRI-targeted biopsy on pre-therapeutic risk assessment in prostate cancer patients candidate for radical prostatectomy.

PURPOSE: To assess the current status and future potential of multiparametric MRI (mpMRI) and MRI-targeted biopsy (MRI-TBx) on the pretherapeutic risk assessment in prostate cancer patients' candidates for radical prostatectomy. METHODS: A literature search of the MEDLINE/PubMed and Scopus database was performed. English-language original and review articles were analyzed and summarized after an interactive peer-review process of the panel. RESULTS: Pretherapeutic risk assessment tools should be based on target plus systematic biopsies, where the addition of systematic biopsy (TRUS-Bx) to the mpMRI-target cores is associated with a lower rate of upgrading at final pathology. The combination of mpMRI findings with clinical parameters outperforms models based on clinical parameters alone in the prediction of adverse pathological outcomes and oncological results. This is particularly true when a specialized radiologist is present. CONCLUSION: The combination of mpMRI findings and clinical parameters should be considered to improve patient stratification in the pretherapeutic risk assessment. There is an urgent need to develop or include MRI data and MRI-TBx findings in available preoperative risk tools. This will allow improving the pretherapeutic risk assessment, providing important additional information for patient-tailored treatment planning and optimizing outcomes.

Comparisons between magnetic resonance/ultrasound fusion-guided biopsy and standard biopsy in the diagnosis of prostate cancer: A prospective cohort study.

Prostate-specific antigen is not useful for detection of prostate cancer in Chinese men. The major problems in prostate cancer patients are overdiagnosis and overtreatment. The objective of the study was to test the hypothesis that targeted biopsy is an accurate diagnostic tool for prostate cancer detection than standard biopsy in Chinese men.Total, 998 patients whom multiparticulate multiparametric magnetic resonance imaging had revealed at least 1 lesion in the prostate were included in a cohort. Patients were subjected to magnetic resonance imaging (MRI)/ultrasound (US) fusion-guided biopsy followed US-guided biopsy. Benefits of a diagnostic test were evaluated by decision curve analysis. Patients who were diagnosed as having prostate cancer by either of biopsies were subjected to radical prostatectomies followed by whole-mounted pathology (n = 578). Spearman rank correlation was performed between the biopsy results and the subtype of prostate cancer at 99% of confidence level.With respect to whole-mounted pathology, for US-guided biopsy, MRI/US fusion-guided biopsy, and combined data of both biopsies, sensitivities were 0.973, 0.983, and 0.973 and accuracies were 0.837, 0.91, and 0.917, respectively. MRI/US fusion-guided biopsy (P = .165) and combined data of both biopsies (P = .182) had the same specificity to whole-mount pathology. However, a US-guided biopsy had not the same specificity to whole-mount pathology (P = .0003). Decision-making zones for radical prostatectomy of different biopsies were in the order of combined data of both biopsies >MRI/US fusion-guided biopsy >US-guided biopsy.Only the targeted biopsy is recommended for the diagnosis of prostate cancer.

Litigation claims in relation to radiology: what can we learn?

AIM: To analyse data provided by the National Health Service Litigation Authority (NHSLA) to establish common and/or reoccurring themes or trends, and use these established learning points to reduce the possibility of such claims in the future. MATERIALS AND METHODS: Data provided by the NHSLA under the Freedom of Information Act for settled claims against radiology between 1995 and 2014 were analysed for common themes. RESULTS: Seven hundred and ninety-one settled claims were recorded by the NHSLA between 1995 and 2014 where radiology was implicated as the primary specialty at fault. Alleged missed or delayed diagnosis of a tumour accounted for almost a third of claims. Eight percent of claims related to interventional radiology. Almost 10% of claims (n=75) were settled due to an injury whilst in the radiology department, with almost a third of these due to a fall in the department. CONCLUSION: "To err is human", but by analysing NHSLA claims related to radiology, thematic analysis and discussion regarding these cases can be highlighted, and hopefully, to mitigate these risks and thus reduce liability in the future.

Magnetic Resonance-Guided Focused Ultrasound Neurosurgery for Essential Tremor: A Health Technology Assessment.

BACKGROUND: The standard treatment option for medication-refractory essential tremor is invasive neurosurgery. A new, noninvasive alternative is magnetic resonance-guided focused ultrasound (MRgFUS) neurosurgery. We aimed to determine the effectiveness, safety, and cost-effectiveness of MRgFUS neurosurgery for the treatment of moderate to severe, medication-refractory essential tremor in Ontario. We also spoke with people with essential tremor to gain an understanding of their experiences and thoughts regarding treatment options, including MRgFUS neurosurgery. METHODS: We performed a systematic review of the clinical literature published up to April 11, 2017, that examined MRgFUS neurosurgery alone or compared with other interventions for the treatment of moderate to severe, medication-refractory essential tremor. We assessed the risk of bias of each study and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic review of the economic literature and created Markov cohort models to assess the cost-effectiveness of MRgFUS neurosurgery compared with other treatment options, including no surgery. We also estimated the budget impact of publicly funding MRgFUS neurosurgery in Ontario for the next 5 years. To contextualize the potential value of MRgFUS neurosurgery as a treatment option for essential tremor, we spoke with people with essential tremor and their families. RESULTS: Nine studies met our inclusion criteria for the clinical evidence review. In noncomparative studies, MRgFUS neurosurgery was found to significantly improve tremor severity and quality of life and to significantly reduce functional disability (GRADE: very low). It was also found to be significantly more effective than a sham procedure (GRADE: high). We found no significant difference in improvements in tremor severity, functional disability, or quality of life between MRgFUS neurosurgery and deep brain stimulation (GRADE: very low). We found no significant difference in improvement in tremor severity compared with radiofrequency thalamotomy (GRADE: low). MRgFUS neurosurgery has a favourable safety profile.We estimated that MRgFUS neurosurgery has a mean cost of $23,507 and a mean quality-adjusted survival of 3.69 quality-adjusted life-years (QALYs). We also estimated that the mean costs and QALYs of radiofrequency thalamotomy and deep brain stimulation are $14,978 and 3.61 QALYs, and $57,535 and 3.94 QALYs, respectively. For people ineligible for invasive neurosurgery, we estimated the incremental cost-effectiveness ratio (ICER) of MRgFUS neurosurgery compared with no surgery as $43,075 per QALY gained. In people eligible for invasive neurosurgery, the ICER of MRgFUS neurosurgery compared with radiofrequency thalamotomy is $109,795 per QALY gained; when deep brain stimulation is compared with MRgFUS neurosurgery, the ICER is $134,259 per QALY gained. Of note however, radiofrequency thalamotomy is performed very infrequently in Ontario. We also estimated that the budget impact of publicly funding MRgFUS neurosurgery in Ontario at the current case load (i.e., 48 cases/year) would be about $1 million per year for the next 5 years.People with essential tremor who had undergone MRgFUS neurosurgery reported positive experiences with the procedure. The tremor reduction they experienced improved their ability to perform activities of daily living and improved their quality of life. CONCLUSIONS: MRgFUS neurosurgery is an effective and generally safe treatment option for moderate to severe, medication-refractory essential tremor. It provides a treatment option for people ineligible for invasive neurosurgery and offers a noninvasive option for all people considering neurosurgery.For people ineligible for invasive neurosurgery, MRgFUS neurosurgery is cost-effective compared with no surgery. In people eligible for invasive neurosurgery, MRgFUS neurosurgery may be one of several reasonable options. Publicly funding MRgFUS neurosurgery for the treatment of moderate to severe, medication-refractory essential tremor in Ontario at the current case load would have a net budget impact of about $1 million per year for the next 5 years.People with essential tremor who had undergone MRgFUS neurosurgery reported positive experiences. They liked that it was a noninvasive procedure and reported a substantial reduction in tremor that resulted in an improvement in their quality of life.

Technical Note: Experimental verification of magnetic field-induced beam deflection and Bragg peak displacement for MR-integrated proton therapy.

PURPOSE: Given its sensitivity to anatomical variations, proton therapy is expected to benefit greatly from integration with magnetic resonance imaging for online anatomy monitoring during irradiation. Such an integration raises several challenges, as both systems mutually interact. The proton beam will experience quasi-continuous energy loss and energy-dependent electromagnetic deflection at the same time, giving rise to a deflected beam trajectory and an altered dose distribution with a displaced Bragg peak. So far, these effects have only been predicted using Monte Carlo and analytical models, but no clear consensus has been reached and experimental benchmark data are lacking. We measured proton beam trajectories and Bragg peak displacement in a homogeneous phantom placed inside a magnetic field and compared them to simulations. METHODS: Planar dose distributions of proton pencil beams (80-180 MeV) traversing the field of a 0.95 T NdFeB permanent magnet while depositing energy in a PMMA slab phantom were measured using EBT3 radiochromic films and simulated using the Geant4 toolkit. Deflected beam trajectories and the Bragg peak displacement were extracted from the measured planar dose distributions and compared against the simulations. RESULTS: The lateral beam deflection was clearly visible on the EBT3 films and ranged from 1 to 10 mm for 80 to 180 MeV, respectively. Simulated and measured beam trajectories and Bragg peak displacement agreed within 0.8 mm for all studied proton energies. CONCLUSIONS: These results prove that the magnetic field-induced Bragg peak displacement is both measurable and accurately predictable in a homogeneous phantom at 0.95 T, and allows Monte Carlo simulations to be used as gold standard for proton beam trajectory prediction in similar frameworks for MR-integrated proton therapy.

Remote Cherenkov imaging-based quality assurance of a magnetic resonance image-guided radiotherapy system.

PURPOSE: Tools to perform regular quality assurance of magnetic resonance image-guided radiotherapy (MRIgRT) systems should ideally be independent of interference from the magnetic fields. Remotely acquired optical Cherenkov imaging-based dosimetry measurements in water were investigated for this purpose, comparing measures of dose accuracy, temporal dynamics, and overall integrated IMRT delivery. METHODS: A 40 × 30.5 × 37.5 cm3 water tank doped with 1 g/L of quinine sulfate was imaged using an intensified charge-coupled device (ICCD) to capture the Cherenkov emission while being irradiated by a commercial MRIgRT system (ViewRay™). The ICCD was placed down-bore at the end of the couch, 4 m from treatment isocenter and behind the 5-Gauss line of the 0.35-T MRI. After establishing optimal camera acquisition settings, square beams of increasing size (4.2 × 4.2 cm2 , 10.5 × 10.5 cm2 , and 14.7 × 14.7 cm2 ) were imaged at 0.93 frames per second, from an individual cobalt-60 treatment head, to develop projection measures related to percent depth dose (PDD) curves and cross beam profiles (CPB). These Cherenkov-derived measurements were compared to ionization chamber (IC) and radiographic film dosimetry data, as well as simulation data from the treatment planning system (TPS). An intensity-modulated radiotherapy (IMRT) commissioning plan from AAPM TG-119 (C4:C-Shape) was also imaged at 2.1 frames per second, and the single linear sum image from 509 s of plan delivery was compared to the dose volume prediction generated by the TPS using gamma index analysis. RESULTS: Analysis of standardized test target images (1024 × 1024 pixels) yielded a pixel resolution of 0.37 mm/pixel. The beam width measured from the Cherenkov image-generated projection CBPs was within 1 mm accuracy when compared to film measurements for all beams. The 502 point measurements (i.e., pixels) of the Cherenkov image-based projection percent depth dose curves (pPDDs) were compared to pPDDs simulated by the treatment planning system (TPS), with an overall average error of 0.60%, 0.56%, and 0.65% for the 4.2, 10.5, and 14.7 cm square beams, respectively. The relationships between pPDDs and central axis PDDs derived from the TPS were used to apply a weighting factor to the Cherenkov pPDD, so that the Cherenkov data could be directly compared to IC PDDs (average error of -0.07%, 0.10%, and -0.01% for the same sized beams, respectively). Finally, the composite image of the TG-119 C4 treatment plan achieved a 95.1% passing rate using 4%/4 mm gamma index agreement criteria between Cherenkov intensity and TPS dose volume data. CONCLUSIONS: This is the first examination of Cherenkov-generated pPDDs and pCBPs in an MR-IGRT system. Cherenkov imaging measurements were fast to acquire, and minimal error was observed overall. Cherenkov imaging also provided novel real-time data for IMRT QA. The strengths of this imaging are the rapid data capture ability providing real-time, high spatial resolution data, combined with the remote, noncontact nature of imaging. The biggest limitation of this method is the two-dimensional (2D) projection-based imaging of three-dimensional (3D) dose distributions through the transparent water tank.

Cost-effectiveness of magnetic resonance imaging and targeted fusion biopsy for early detection of prostate cancer.

OBJECTIVE: To determine how best to use magnetic resonance imaging (MRI) and targeted MRI/ultrasonography fusion biopsy for early detection of prostate cancer (PCa) in men with elevated prostate-specific antigen (PSA) concentrations and whether it can be cost-effective. METHODS: A Markov model of PCa onset and progression was developed to estimate the health and economic consequences of PCa screening with MRI. Patients underwent PSA screening from ages 55 to 69 years. Patients with elevated PSA concentrations (>4 ng/mL) underwent MRI, followed by targeted fusion or combined (standard + targeted fusion) biopsy on positive MRI, and standard or no biopsy on negative MRI. Prostate Imaging Reporting and Data System (PI-RADS) score on MRI was used to determine biopsy decisions. Deaths averted, quality-adjusted life-years (QALYs), cost and incremental cost-effectiveness ratio (ICER) were estimated for each strategy. RESULTS: With a negative MRI, standard biopsy was more expensive and had lower QALYs than performing no biopsy. The optimum screening strategy (ICER $23 483/QALY) recommended combined biopsy for patients with PI-RADS score ≥3 and no biopsy for patients with PI-RADS score <3, and reduced the number of screening biopsies by 15%. Threshold analysis suggests MRI continues to be cost-effective when the sensitivity and specificity of MRI and combined biopsy are simultaneously reduced by 19 percentage points. CONCLUSIONS: Our analysis suggests MRI followed by targeted MRI/ultrasonography fusion biopsy can be a cost-effective approach to the early detection of PCa.

Targeted biopsy: benefits and limitations.

PURPOSE OF REVIEW: To review the current literature regarding the role of multiparametric MRI and fusion-guided biopsies in urologic practice. RECENT FINDINGS: Fusion biopsies consistently show an increase in the detection of clinically significant cancers and decrease in low-risk disease that may be more suitable for active surveillance. Although, when to incorporate multiparametric MRI into workup is not clearly agreed upon, studies have shown a clear benefit in both biopsy naïve and those with prior negative biopsies in determining the appropriate treatment strategy. More recently, cost-analysis models have been published that show that upfront MRIs are more cost-effective when considering missed cancers and treatment courses. SUMMARY: With improved accuracy over systematic biopsies, fusion biopsies are a superior method for detection of the true grade of cancer for both biopsy naïve and patients with prior negative biopsies, choosing appropriate candidates for active surveillance, and monitoring progression on active surveillance.

Prostate Cancer Risk Assessment in Biopsy-naïve Patients: The Rotterdam Prostate Cancer Risk Calculator in Multiparametric Magnetic Resonance Imaging-Transrectal Ultrasound (TRUS) Fusion Biopsy and Systematic TRUS Biopsy.

BACKGROUND: The value of multiparametric magnetic resonance imaging (mpMRI) and targeted biopsy (TBx) remains controversial for biopsy-naïve men when compared to transrectal ultrasound (TRUS)-guided systematic biopsy (SBx). Risk-based patient selection could help to selectively identify men with significant prostate cancer (PCa) and thus reduce unnecessary mpMRI and biopsies. OBJECTIVES: To compare PCa detection rates for mpMRI TBx with SBx and to determine the rate of potentially avoided mpMRI and biopsies through risk-based selection using the Rotterdam Prostate Cancer Risk Calculator (RPCRC). DESIGN, SETTING, AND PARTICIPANTS: Two-hundred consecutive biopsy-naïve men in two centres underwent mpMRI scanning, 12-core SBx, and subsequent MRI-TRUS TBx in the case of suspicious lesion(s) (Prostate Imaging-Reporting and Data System v.2 score ≥3). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured the detection rate for high-grade (Gleason score ≥ 3+4) PCa for TBx and SBx. We carried out a retrospective stratification according to RPCRC biopsy advice to determine the rate of mpMRI and biopsies that could potentially be avoided by RPCRC-based patient selection in relation to the rate of high-grade PCa missed. RESULTS AND LIMITATIONS: TBx yielded high-grade PCa in 51 men (26%) and low-grade PCa in 14 men (7%), while SBx yielded high-grade PCa in 63 men (32%) and low-grade PCa in 41 men (21%). Four out of 73 men (5%) with negative RPCRC advice and 63 out of 127 men (50%) with positive advice had high-grade PCa. Upfront RPCRC-based patient selection for mpMRI and TBx would have avoided 73 out of 200 (37%) mpMRI scans, missing two out of 51 (4%) high-grade PCas. Limitations include the RPCRC definition of high- and low-grade PCa and different mpMRI techniques. CONCLUSIONS: mpMRI with TBx detected PCa with high Gleason score and avoided biopsy in low-grade PCa, but failed to detect all high-grade PCa when compared to SBx among biopsy-naïve men. Risk-based patient selection using the RPCRC can avoid one-third of mpMRI scans and SBx in biopsy-naïve men. PATIENT SUMMARY: Men with a suspicion of prostate cancer are increasingly undergoing a magnetic resonance imaging (MRI) scan. Although promising, MRI-targeted biopsy is not accurate enough to safely replace systematic prostate biopsy for now. Individualised assessment of prostate cancer risk using the Rotterdam Prostate Cancer Risk Calculator could avoid one-third of MRI scans and systematic prostate biopsies.

Clinical Utility of Multiparametric Magnetic Resonance Imaging as the First-line Tool for Men with High Clinical Suspicion of Prostate Cancer.

BACKGROUND: Transrectal ultrasound-guided biopsy (TRUS-Bx) is recommended by the European Urology Association (EAU) as the first diagnostic modality for men at risk of prostate cancer (PCa). Current EAU guidelines reserve the use of multiparametric MRI to target or guide any repeat biopsy (mpMRI-Bx). It remains uncertain if TRUS-Bx is effective as a first strategy in terms of costs, diagnostic performance, time to diagnosis, and triage for individualised therapy. OBJECTIVE: To determine the diagnostic and treatment costs and the effectiveness of pathways incorporating mpMRI-Bx compared to TRUS-Bx in men at high risk of PCa. DESIGN, SETTING, AND PARTICIPANTS: A cost and time analysis was performed using data from a randomised single-centre study of 1140 patients (prostate-specific antigen >4ng/ml) divided into two groups: 570 patients underwent an initial TRUS-Bx and 570 underwent 3-T mpMRI-Bx. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Budget analyses were used to compare the diagnostic strategies using reimbursement data from the Italian National Health Security system. Analyses of reimbursable diagnostic and treatment costs were undertaken separately. Histologic outcomes, pathway diagnostic accuracy, therapy choices, and time to diagnosis were compared. RESULTS AND LIMITATIONS: The cumulative diagnosis costs were 14.6% greater for the mpMRI-Bx pathway than for the TRUS strategy, and 5.2-6.0% higher for therapy. Diagnostic costs were €228 946 for mpMRI-Bx and €199 750 for TRUS-Bx, and the corresponding therapy costs were €1 912 000 and €1 802 800. The mpMRI-Bx strategy was highly effective in excluding clinically significant disease (Gleason ≥7; sensitivity and negative predictive value both 100%, 95% confidence interval 98-100%). The time to diagnosis was significantly shorter for the mpMRI-Bx (median 4.0 mo interquartile range [IQR] 3-6) than for the TRUS-Bx strategy (median 6 mo, IQR 4-12; p<0.001). Limitations include the lack of data on costs associated with treatment-related complications and follow-up data. CONCLUSIONS: The mpMRI-Bx strategy is effective for diagnosing patients with a clinical suspicion of PCa and provides more accurate diagnosis, with combined diagnosis and therapy costs only moderately higher than for the standard strategy. PATIENT SUMMARY: It is a matter of debate whether a diagnostic pathway that incorporates multiparametric magnetic resonance imaging (MRI) as the first-line test before performing any type of biopsy in men suspected of having prostate cancer (PCa) is cost-effective. Our analysis of the costs for men suspected of harbouring PCa revealed higher diagnostic costs for the MRI approach, with the benefits of greater diagnostic accuracy. Moreover, the combined diagnostic and treatment costs are only modestly higher whenever the same treatment for all patients is considered.