Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA.

Functional renal magnetic resonance imaging (MRI) has seen a number of recent advances, and techniques are now available that can generate quantitative imaging biomarkers with the potential to improve the management of kidney disease. Such biomarkers are sensitive to changes in renal blood flow, tissue perfusion, oxygenation and microstructure (including inflammation and fibrosis), processes that are important in a range of renal diseases including chronic kidney disease. However, several challenges remain to move these techniques towards clinical adoption, from technical validation through biological and clinical validation, to demonstration of cost-effectiveness and regulatory qualification. To address these challenges, the European Cooperation in Science and Technology Action PARENCHIMA was initiated in early 2017. PARENCHIMA is a multidisciplinary pan-European network with an overarching aim of eliminating the main barriers to the broader evaluation, commercial exploitation and clinical use of renal MRI biomarkers. This position paper lays out PARENCHIMA's vision on key clinical questions that MRI must address to become more widely used in patients with kidney disease, first within research settings and ultimately in clinical practice. We then present a series of practical recommendations to accelerate the study and translation of these techniques.

Optimising preoperative risk stratification tools for prostate cancer using mpMRI.

PURPOSE: To improve preoperative risk stratification for prostate cancer (PCa) by incorporating multiparametric MRI (mpMRI) features into risk stratification tools for PCa, CAPRA and D'Amico. METHODS: 807 consecutive patients operated on by robot-assisted radical prostatectomy at our institution during the period 2010-2015 were followed to identify biochemical recurrence (BCR). 591 patients were eligible for final analysis. We employed stepwise backward likelihood methodology and penalised Cox cross-validation to identify the most significant predictors of BCR including mpMRI features. mpMRI features were then integrated into image-adjusted (IA) risk prediction models and the two risk prediction tools were then evaluated both with and without image adjustment using receiver operating characteristics, survival and decision curve analyses. RESULTS: 37 patients suffered BCR. Apparent diffusion coefficient (ADC) and radiological extraprostatic extension (rEPE) from mpMRI were both significant predictors of BCR. Both IA prediction models reallocated more than 20% of intermediate-risk patients to the low-risk group, reducing their estimated cumulative BCR risk from approximately 5% to 1.1%. Both IA models showed improved prognostic performance with a better separation of the survival curves. CONCLUSION: Integrating ADC and rEPE from mpMRI of the prostate into risk stratification tools improves preoperative risk estimation for BCR. KEY POINTS: • MRI-derived features, ADC and EPE, improve risk stratification of biochemical recurrence. • Using mpMRI to stratify prostate cancer patients improves the differentiation between risk groups. • Using preoperative mpMRI will help urologists in selecting the most appropriate treatment.

Dynamic contrast-enhanced MRI measurement of renal function in healthy participants.

Background High repeatability, accuracy, and precision for renal function measurements need to be achieved to establish renal dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a clinically useful diagnostic tool. Purpose To investigate the repeatability, accuracy, and precision of DCE-MRI measured renal perfusion and glomerular filtration rate (GFR) using iohexol-GFR as the reference method. Material and Methods Twenty healthy non-smoking volunteers underwent repeated DCE-MRI and an iohexol-GFR within a period of 10 days. Single-kidney (SK) MRI measurements of perfusion (blood flow, Fb) and filtration (GFR) were derived from parenchymal intensity time curves fitted to a two-compartment filtration model. The repeatability of the SK-MRI measurements was assessed using coefficient of variation (CV). Using iohexol-GFR as reference method, the accuracy of total MR-GFR was determined by mean difference (MD) and precision by limits of agreement (LoA). Results SK-Fb (MR1, 345 ± 84; MR2, 371 ± 103 mL/100 mL/min) and SK-GFR (MR1, 52 ± 14; MR2, 54 ± 10 mL/min/1.73 m2) measurements achieved a repeatability (CV) in the range of 15-22%. With reference to iohexol-GFR, MR-GFR was determined with a low mean difference but high LoA (MR1, MD 1.5 mL/min/1.73 m2, LoA [-42, 45]; MR2, MD 6.1 mL/min/1.73 m2, LoA [-26, 38]). Eighty percent and 90% of MR-GFR measurements were determined within ± 30% of the iohexol-GFR for MR1 and MR2, respectively. Conclusion Good repeatability of SK-MRI measurements and good agreement between MR-GFR and iohexol-GFR provide a high clinical potential of DCE-MRI for renal function assessment. A moderate precision in MR-derived estimates indicates that the method cannot yet be used in clinical routine.

Trends in stage-specific incidence of prostate cancer in Norway, 1980-2010: a population-based study.

OBJECTIVE: To estimate changes in the stage distribution of prostate cancer during the time period where opportunistic prostate-specific antigen (PSA) testing was introduced. PATIENTS AND METHODS: Cancer stage, age, and year of diagnosis were obtained for all men aged >50 years diagnosed with prostate cancer in Norway during the period 1980-2010. Three calendar-time periods (1980-1989, 1990-2000, and 2001-2010) and three age groups (50-65, 66-74, and ≥75 years) were defined. Birth cohorts were categorised into four intervals: ≤1915, 1916-1925, 1926-1940 and ≥1941. We used Poisson regressions to conduct both a time period and cohort-based analysis of trends in the incidence of localised, regional, and distant cancer for each combination of age groups and calendar-time periods or birth cohorts, respectively. Additionally, we explored the effect of cohorts on the stage-specific incidence graphically with a Poisson regression using 5-year age groups, and by estimating cumulative incidence rates for each birth cohort. RESULTS: The annual incidence of localised cancers among men aged 50-65 and 66-74 years rose from 41.4 and 255.2 per 100 000, respectively, before the introduction of PSA testing to 137.9 and 418.7 in 2001-2010 afterwards, corresponding to 3.3 [95% confidence interval (CI) 3.1-3.5] and 1.6 (95% CI 1.6-1.7) fold increases. The incidence of regional cancers increased by a factor seven among men aged <75 years. The incidence of distant cancers in men aged ≥75 years decreased by 29% (95% CI 25-33%). These findings were confirmed in the cohort-based approach. CONCLUSION: Opportunistic PSA testing substantially increased the incidence of localised and regional prostate cancers among men aged 50-74 years, which was not fully compensated by the 30% decrease in incidence of distant prostate cancers in older men.

Quantification of Single-Kidney Function and Volume in Living Kidney Donors Using Dynamic Contrast-Enhanced MRI.

OBJECTIVE: The objective of our study was to investigate whether dynamic contrast-enhanced MRI (DCE-MRI) can detect differences and potential adaption in single-kidney parenchymal volume, blood flow, glomerular filtration rate (GFR), and filtration fraction in the remaining kidney of healthy donors compared with nondonors. Further, we evaluated the agreement in donor GFRs measured using DCE-MRI versus serum clearance of iohexol. SUBJECTS AND METHODS: Twenty living kidney donors and 20 healthy control subjects underwent DCE-MRI and iohexol GFR. Renal parenchymal volume was assessed from maximum-signal-intensity maps. Single-kidney MRI measurements of blood flow and GFR were derived from parenchymal signal intensity-time curves fitted to a two-compartment filtration model. The Student t test, Pearson correlation coefficient, mean differences, and limits of agreement were applied to analyze MRI measurements between groups and agreement with iohexol GFR. RESULTS: MRI findings showed significantly higher blood flow (difference in mean values of donors vs control subjects, 54%; p = 0.001), GFR (78%, p < 0.0001), and renal parenchymal volume (65%, p < 0.0001) in the single kidney of donors compared with the single kidney of healthy control subjects. In the donors, a proportional increase in blood flow and GFR resulted in a comparable filtration fraction, as was observed in the control subjects. Significant correlations were found between MRI-derived GFR and parenchymal volume (p < 0.0016) as well as with iohexol GFR (p < 0.0001). The mean difference between MRI-derived GFR and iohexol GFR was 14.0 mL/min, and the limits of agreement between MRI-derived GFR and iohexol GFR were -24.1 and 52.1 mL/min. CONCLUSION: DCE-MRI-derived values for single-kidney function and volume in kidney donors were significantly higher than those in control subjects and suggest a future potential benefit of DCE-MRI for diagnostic and prognostic structural and functional assessments in living kidney donors.

Use of 3D DCE-MRI for the estimation of renal perfusion and glomerular filtration rate: an intrasubject comparison of FLASH and KWIC with a comprehensive framework for evaluation.

OBJECTIVE. The purpose of this article is to compare two 3D dynamic contrast-enhanced (DCE) MRI measurement techniques for MR renography, a radial k-space weighted image contrast (KWIC) sequence and a cartesian FLASH sequence, in terms of intrasubject differences in estimates of renal functional parameters and image quality characteristics. SUBJECTS AND METHODS. Ten healthy volunteers underwent repeated breath-hold KWIC and FLASH sequence examinations with temporal resolutions of 2.5 and 2.8 seconds, respectively. A two-compartment model was used to estimate MRI-derived perfusion parameters and glomerular filtration rate (GFR). The latter was compared with the iohexol GFR and the estimated GFR. Image quality was assessed using a visual grading characteristic analysis of relevant image quality criteria and signal-to-noise ratio calculations. RESULTS. Perfusion estimates from FLASH were closer to literature reference values than were the KWIC sequences. In relation to the iohexol GFR (mean [± SD], 103 ± 11 mL/min/1.73 m(2)), KWIC produced significant underestimations and larger bias in GFR values (mean, 70 ± 30 mL/min/1.73 m(2); bias = -33.2 mL/min/1.73 m(2)) compared with the FLASH GFR (110 ± 29 mL/min/1.73 m(2); bias = 6.4 mL/min/1.73 m(2)). KWIC was statistically significantly (p < 0.005) more impaired by artifacts than was FLASH (AUC = 0.18). The average signal-enhancement ratio (delta ratio) in the cortex was significantly lower for KWIC (delta ratio = 0.99) than for FLASH (delta ratio = 1.40). Other visually graded image quality characteristics and signal-to-noise ratio measurements were not statistically significantly different. CONCLUSION. Using the same postprocessing scheme and pharmacokinetic model, FLASH produced more accurate perfusion and filtration parameters than did KWIC compared with clinical reference methods. Our data suggest an apparent relationship between image quality characteristics and the degree of stability in the numeric model-based renal function estimates.

1.5-T multiparametric MRI using PI-RADS: a region by region analysis to localize the index-tumor of prostate cancer in patients undergoing prostatectomy.

BACKGROUND: The use of multiparametric magnetic resonance imaging (mpMRI) to detect and localize prostate cancer has increased in recent years. In 2010, the European Society of Urogenital Radiology (ESUR) published guidelines for mpMRI and introduced the Prostate Imaging Reporting and Data System (PI-RADS) for scoring the different parameters. PURPOSE: To evaluate the reliability and diagnostic performance of endorectal 1.5-T mpMRI using the PI-RADS to localize the index tumor of prostate cancer in patients undergoing prostatectomy. MATERIAL AND METHODS: This institutional review board IRB-approved, retrospective study included 63 patients (mean age, 60.7 years, median PSA, 8.0). Three observers read mpMRI parameters (T2W, DWI, and DCE) using the PI-RADS, which were compared with the results from whole-mount histopathology that analyzed 27 regions of interest. Inter-observer agreement was calculated as well as sensitivity, specificity, positive predictive value (PPV), and negative predicted value (NPV) by dichotomizing the PI-RADS criteria scores ≥3. A receiver-operating curve (ROC) analysis was performed for the different MR parameters and overall score. RESULTS: Inter-observer agreement on the overall score was 0.41. The overall score in the peripheral zone achieved sensitivities of 0.41, 0.60, and 0.55 with an NPV of 0.80, 0.84, and 0.83, and in the transitional zone, sensitivities of 0.26, 0.15, and 0.19 with an NPV of 0.92, 0.91, and 0.92 for Observers 1, 2, and 3, respectively. The ROC analysis showed a significantly increased area under the curve (AUC) for the overall score when compared to T2W alone for two of the three observers. CONCLUSION: 1.5 T mpMRI using the PI-RADS to localize the index tumor achieved moderate reliability and diagnostic performance.

Standard 1.5-T MRI of endometrial carcinomas: modest agreement between radiologists.

OBJECTIVES: To evaluate pelvic magnetic resonance imaging (MRI) interobserver agreement for the detection of deep myometrial invasion, cervical stroma invasion and lymph node metastases in endometrial carcinoma patients in relation to surgical staging. METHODS: Fifty-seven patients with histologically confirmed endometrial carcinoma were prospectively included in a study of preoperative 1.5-T MRI. Four radiologists, blinded to patient data, independently reviewed the images for the presence of deep myometrial invasion, cervical stroma invasion and lymph node metastases. Kappa coefficients for interobserver agreement and diagnostic performances for each observer were calculated using final surgical staging results (FIGO 09) as reference standard. RESULTS: Overall agreement among all observers was moderate for cervical stroma invasion (κ = 0.50 [95% CI 0.27-0.73]) and lymph node metastases (κ = 0.56 [0.09-0.80]) and fair for deep myometrial invasion (κ = 0.39 [0.26-0.55]). Sensitivity (specificity) values for the four observers were 72-92% (44-63%) for deep myometrial invasion, 38-63% (82-94%) for cervical stroma invasion and 25-38% (90-100%) for lymph node metastases. CONCLUSIONS: Conventional MRI showed only modest interobserver agreement and diagnostic accuracy for detection of deep myometrial invasion, cervical stroma invasion and lymph node metastases. Improved methods are needed for preoperative imaging in the staging of endometrial carcinomas. KEY POINTS: MRI is an important tool for preoperative endometrial cancer staging. • Staging agreement based on pelvic MRI was modest among different observers. • Preoperative MRI alone was suboptimal in identifying high-risk patients. • Improved imaging and biomarkers may refine preoperative risk stratification in endometrial cancer.

Assessment of kidney volumes from MRI: acquisition and segmentation techniques.

OBJECTIVE: The prevalence of chronic kidney disease (CKD) is increasing worldwide. In Europe alone, at least 8% of the population currently has some degree of CKD. CKD is associated with serious comorbidity, reduced life expectancy, and high economic costs; hence, early detection and adequate treatment of kidney disease are important. CONCLUSION: We review state-of-the-art MRI acquisition techniques for CKD, with a special focus on image segmentation methods used for the estimation of kidney volume.

High frequency of adrenal myelolipomas and testicular adrenal rest tumours in adult Norwegian patients with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency.

BACKGROUND: Increased frequencies of adrenal tumours and testicular adrenal rest tumours (TART) have been reported in patients with 21-hydroxylase deficiency (21OHD). OBJECTIVE: Patients, methods and design From a cross-sectional population-based study of 101 adult Norwegian patients with 21OHD, sixty-two participated in this study (23 men, 39 women; age range 18-75); thirty-two were salt wasting (SW) and 30 simple virilizing (SV); they were assessed with adrenal computed tomography (CT), testicular ultrasound and hormone measurement in the morning after overnight medication fast. RESULTS: Nine adrenal tumours were detected in seven (11%) patients (bilateral in 2); four were myelolipomas and one a phaeochromocytoma. Seventeen (27%) had normal adrenal size, whereas 36 (58%) had persisting hyperplasia, and seven (11%) adrenal hypoplasia. Abnormal adrenals were more common in SW than in SV. TART occurred exclusively in SW and was present in seven (57%) of these men. Testicular volumes were small compared with normative data. Morning ACTH and 17-hydroxyprogesterone levels correlated positively with adrenal dimensions and frequency of TART. CONCLUSION: In this unselected population of patients with classical 21OHD, we found high frequencies of adrenal tumours, particularly myelolipomas, and of hyperplasia and hypoplasia, and TART in SW. It is important that physicians are aware that benign adrenal and testicular tumours occur frequently in 21OHD. Furthermore, these findings may reflect inappropriate glucocorticoid therapy, making a case for the advancement of novel physiological treatment modalities.

MRI of the transverse and alar ligaments in rheumatoid arthritis: feasibility and relations to atlantoaxial subluxation and disease activity.

INTRODUCTION: Dysfunctional transverse and alar craniovertebral ligaments can cause instability and osseous destruction in rheumatoid arthritis (RA). This study examined (1) the feasibility of high-resolution magnetic resonance imaging (MRI) of these ligaments in RA and (2) the relation between ligament high-signal changes and atlantoaxial subluxation and RA duration/severity. METHODS: Consecutive RA patients (n=46) underwent clinical examination, functional radiography, and high-resolution MRI. Two blinded radiologists rated MRI image quality, graded ligament high-signal changes 0-3 on proton-weighted sequences using an existing grading system, and assessed cervical spine rheumatic changes on short tau inversion recovery images. Agreement was analyzed using kappa and relations using multiple logistic regression. RESULTS: MRI images had good quality in 42 (91.3%) of 46 patients and were interpretable in 44 (32 women and 12 men, median age/disease duration 60.4/9.1 years). MRI grades 2-3 changes of the transverse and alar ligaments showed moderate and good interobserver agreement (kappa 0.59 and 0.78), respectively, and prevalence 31.8% and 34.1%. Such ligament changes were more frequent with increasing anterior atlantoaxial subluxation (p=0.012 transverse, p=0.028 alar), higher erythrocyte sedimentation rate (p=0.003 transverse), positive rheumatoid factor (p=0.002 alar), and neck pain (p=0.004 alar). CONCLUSION: This first study of high-resolution MRI of these ligaments in RA showed high feasibility and relations with atlantoaxial subluxation, RA disease activity, and neck pain. The clinical usefulness of such MRI needs further evaluation.

Are MRI high-signal changes of alar and transverse ligaments in acute whiplash injury related to outcome?

BACKGROUND: Upper neck ligament high-signal changes on magnetic resonance imaging (MRI) have been found in patients with whiplash-associated disorders (WAD) but also in non-injured controls. The clinical relevance of such changes is controversial. Their prognostic role has never been evaluated. The purpose of this study was to examine if alar and transverse ligament high-signal changes on MRI immediately following the car accident are related to outcome after 12 months for patients with acute WAD grades 1-2. METHODS: Within 13 days after a car accident, 114 consecutive acute WAD1-2 patients without prior neck injury or prior neck problems underwent upper neck high-resolution proton-weighted MRI. High-signal changes of the alar and transverse ligaments were graded 0-3. A questionnaire including the impact of event scale for measuring posttraumatic stress response and questions on patients' expectations of recovery provided clinical data at injury. At 12 months follow-up, 111 (97.4%) patients completed the Neck Disability Index (NDI) and an 11-point numeric rating scale (NRS-11) on last week neck pain intensity. Factors potentially related to these outcomes were assessed using multiple logistic regression analyses. RESULTS: Among the 111 responders (median age 29.8 years; 63 women), 38 (34.2%) had grades 2-3 alar ligament changes and 25 (22.5%) had grades 2-3 transverse ligament changes at injury. At 12 months follow-up, 49 (44.1%) reported disability (NDI > 8) and 23 (20.7%) neck pain (NRS-11 > 4). Grades 2-3 ligament changes in the acute phase were not related to disability or neck pain at 12 months. More severe posttraumatic stress response increased the odds for disability (odds ratio 1.46 per 10 points on the impact of event scale, p = 0.007) and so did low expectations of recovery (odds ratio 4.66, p = 0.005). CONCLUSIONS: High-signal changes of the alar and transverse ligaments close after injury did not affect outcome for acute WAD1-2 patients without previous neck problems. High-resolution upper neck MRI has limited value for the initial examination and follow-up of such patients.

MRI of the alar and transverse ligaments in whiplash-associated disorders (WAD) grades 1-2: high-signal changes by age, gender, event and time since trauma.

INTRODUCTION: This study describes the prevalence of high-signal changes at magnetic resonance imaging (MRI) of the alar and transverse ligaments in whiplash-associated disorders (WAD) grades 1-2 in relation to age, gender, spinal degeneration, type of trauma event and time since trauma. MATERIALS AND METHODS: In 1,266 consecutive WAD1-2 patients (779 women, 487 men; mean age 42 years) referred from clinicians, high-signal changes in the alar and transverse ligaments at high-resolution proton-weighted MRI were prospectively graded 0-3 based on a previously reported, reliable grading system. Type of event according to The International Statistical Classification of Diseases and Related Health Problems and time of trauma were obtained from referral letters. RESULTS: MRI showed grades 2-3 alar ligament changes in 449 (35.5%; 95% confidence interval (CI), 32.8 to 38.1%) and grades 2-3 transverse ligament changes in 311 (24.6%; 95% CI, 22.2% to 26.9%) of the 1,266 patients. Grades 2-3 changes were more common in men than women, odds ratio 1.9 (95% CI, 1.5 to 2.5) for alar and 1.5 (95% CI, 1.1 to 2.0) for transverse ligament changes. High-signal changes were not related to age, spinal degeneration, type of trauma event or time since trauma (median 5 years). Unilateral changes were more often left- than right-sided. CONCLUSIONS: High-signal changes of the alar and transverse ligaments are common in WAD1-2 and unlikely to represent age-dependent degeneration. Their male and left-side preponderance cannot be explained by variation in ligament stretching or image artefacts. Further studies are needed to clarify whether such changes are caused by trauma.

Blood flow quantification from 2D phase contrast MRI in renal arteries using an unsupervised data driven approach.

We present a clustering approach to segment the renal artery from 2D PC Cine MR images to measure arterial blood velocity and flow. Such information is important in grading renal artery stenosis and to support the decision on surgical interventions like percutaneous transluminal angioplasty. Results from 20 data sets (3 volunteers, 7 patients) show that the renal arteries could be extracted automatically and the corresponding velocity profiles were close (r = 0.977) to that obtained by manual delineations of the vessel areas.

In Vivo Detection of Chronic Kidney Disease Using Tissue Deformation Fields From Dynamic MR Imaging.

OBJECTIVE: Chronic kidney disease (CKD) is a serious medical condition characterized by gradual loss of kidney function. Early detection and diagnosis is mandatory for adequate therapy and prognostic improvement. Hence, in the current pilot study we explore the use of image registration methods for detecting renal morphologic changes in patients with CKD. METHODS: Ten healthy volunteers and nine patients with presumed CKD underwent dynamic T1 weighted imaging without contrast agent. From real and simulated dynamic time series, kidney deformation fields were estimated using a poroelastic deformation model. From the deformation fields several quantitative parameters reflecting pressure gradients, and volumetric and shear deformations were computed. Eight of the patients also underwent a kidney biopsy as a gold standard. RESULTS: We found that the absolute deformation, normalized volume changes, as well as pressure gradients correlated significantly with arteriosclerosis from biopsy assessments. Furthermore, our results indicate that current image registration methodologies are lacking sensitivity to recover mild changes in tissue stiffness. CONCLUSION: Image registration applied to dynamic time series correlated with structural renal changes and should be further explored as a tool for invasive measurements of arteriosclerosis. SIGNIFICANCE: Under the assumption that the proposed framework can be further developed in terms of sensitivity and specificity, it can provide clinicians with a non-invasive tool of high spatial coverage available for characterization of arteriosclerosis and potentially other pathological changes observed in chronic kidney disease.

Dynamic contrast enhanced magnetic resonance imaging of bladder cancer and implications for biological image-adapted radiotherapy.

PURPOSE: To assess the role of image parameters derived from dynamic contrast enhanced magnetic resonance imaging (DCEMRI) in bladder cancer staging, and to investigate the potential use of such parameter images in biological image-adapted radiotherapy (RT). MATERIALS AND METHODS: High-resolution volumetric interpolated breath-hold (VIBE) DCEMRI of 26 patients diagnosed with bladder cancer was performed. DCEMRI parameters derived from tumor and muscle contrast uptake curves were extracted and subjected to correlation analysis with tumor volume as well as clinical, pathological, histological and T2-weighted MR tumor stage. For parameters showing a significant correlation with tumor stage, 3D malignancy maps were generated. As an initial step towards delivery of biologically adapted intensity modulated radiotherapy (IMRT) it was hypothesized that the malignancy map could be used as a RT dose prescription map. Simulating IMRT delivery with multi-leaf collimators (MLCs), idealized dose distributions, constituted by dose cubes, were adapted to the prescription map. The size of the dose cubes were varied to mimic MLCs of varying leaf width. The difference between the adapted and prescribed dose distributions was quantified by the root mean square deviation (RMSD). RESULTS: No significant relationships were found between tumor volume and extracted DCEMRI parameters. The normalized area between tumor and muscle contrast uptake curves (nABC) evaluated from 0-180 seconds (nABC(180)) and 0-480 s (nABC(480)) correlated significantly with tumor stage (p=0.047 and p=0.035, respectively). Dose prescription maps for 10 patients were generated from the nABC(480). The RMSD between the prescribed and adapted dose distribution decreased with decreasing size of the dose cubes. Large interpatient variations in the RMSD and in the dependence of the RMSD on different dose cube sizes were found. CONCLUSIONS: The nABC(180) and nABC(480) may provide added value in staging of bladder cancer. High-resolution IMRT is required for some patients for optimal adapted RT.

Uncertainty evaluation of image-based tumour control probability models in radiotherapy of prostate cancer using a visual analytic tool.

Functional imaging techniques provide radiobiological information that can be included into tumour control probability (TCP) models to enable individualized outcome predictions in radiotherapy. However, functional imaging and the derived radiobiological information are influenced by uncertainties, translating into variations in individual TCP predictions. In this study we applied a previously developed analytical tool to quantify dose and TCP uncertainty bands when initial cell density is estimated from MRI-based apparent diffusion coefficient maps of eleven patients. TCP uncertainty bands of 16% were observed at patient level, while dose variations bands up to 8 Gy were found at voxel level for an iso-TCP approach.

Intensity-based volumetric registration of magnetic resonance images and whole-mount sections of the prostate.

OBJECTIVE: Magnetic Resonance Imaging (MRI) of the prostate provides useful in vivo diagnostic tissue information such as tumor location and aggressiveness, but ex vivo histopathology remains the ground truth. There are several challenges related to the registration of MRI to histopathology. We present a method for registration of standard clinical T2-weighted MRI (T2W-MRI) and transverse histopathology whole-mount (WM) sections of the prostate. METHODS: An isotropic volume stack was created from the WM sections using 2D rigid and deformable registration combined with linear interpolation. The prostate was segmented manually from the T2W-MRI volume and registered to the WM section volume using a combination of affine and deformable registration. The method was evaluated on a set of 12 patients who had undergone radical prostatectomy. Registration accuracy was assessed using volume overlap (Dice Coefficient, DC) and landmark distances. RESULTS: The DC was 0.94 for the whole prostate, 0.63 for the peripheral zone and 0.77 for the remaining gland. The landmark distances were on average 5.4 mm. CONCLUSION: The volume overlap for the whole prostate and remaining gland, as well as the landmark distances indicate good registration accuracy for the proposed method, and shows that it can be highly useful for registering clinical available MRI and WM sections of the prostate.

A biological modelling based comparison of radiotherapy plan robustness using photons vs protons for focal prostate boosting.

BACKGROUND AND PURPOSE: Focal tumour boosting is currently explored in radiotherapy of prostate cancer to increase tumour control. In this study we applied dose response models for both tumour control and normal tissue complications to explore the benefit of proton therapy (PT) combined with focal tumour boosting, also when accounting for inter-fractional motion. MATERIALS AND METHODS: CT scans of seven patients fused with MRI-based index volumes were used. Two volumetric modulated arc therapy (VMAT) plans were created for each patient; one with conventional dose (77 Gy) to the entire prostate, and one with an additional integrated boost (total dose of 95 Gy) to the index lesion. Two corresponding intensity modulated PT (IMPT) plans were created using two lateral opposing spot scanning beams. All plans were evaluated using an MRI-based tumour control probability (TCP) model and normal tissue complication probability (NTCP) models for the rectum and bladder. Plan robustness was evaluated using dose re-calculations on repeat cone-beam CTs. RESULTS: Across all plans, median TCP increased from 86% (range: 59-98%) without boost to 97% (range: 96-99%) with boost. IMPT plans had lower rectum NTCPs (e.g. 3% vs. 4% for boost plans) but higher bladder NTCPs (20% vs. 18% for boost plans), yet only the bladder NTCPs remained different in the cone beam CT-based re-calculations. CONCLUSIONS: Focal tumour boosting can be delivered with either VMAT or protons, and increases the predicted TCP. The small benefit of IMPT when assessing the planned dose distributions was lost when accounting for inter-fractional motion.