Contribution of Dynamic Contrast-enhanced and Diffusion MRI to PI-RADS for Detecting Clinically Significant Prostate Cancer.

Background Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 requires multiparametric MRI of the prostate, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging sequences; however, the contribution of DCE imaging remains unclear. Purpose To assess whether DCE imaging in addition to apparent diffusion coefficient (ADC) and normalized T2 values improves PI-RADS version 2.0 for prediction of clinically significant prostate cancer (csPCa). Materials and Methods In this retrospective study, clinically reported PI-RADS lesions in consecutive men who underwent 3-T multiparametric MRI (T2-weighted, DWI, and DCE MRI) from May 2015 to September 2016 were analyzed quantitatively and compared with systematic and targeted MRI-transrectal US fusion biopsy. The normalized T2 signal (nT2), ADC measurement, mean early-phase DCE signal (mDCE), and heuristic DCE parameters were calculated. Logistic regression analysis indicated the most predictive DCE parameters for csPCa (Gleason grade group ≥2). Receiver operating characteristic parameter models were compared using the Obuchowski test. Recursive partitioning analysis determined ADC and mDCE value ranges for combined use with PI-RADS. Results Overall, 260 men (median age, 64 years [IQR, 58-69 years]) with 432 lesions (csPCa [n = 152] and no csPCa [n = 280]) were included. The mDCE parameter was predictive of csPCa when accounting for the ADC and nT2 parameter in the peripheral zone (odds ratio [OR], 1.76; 95% CI: 1.30, 2.44; P = .001) but not the transition zone (OR, 1.17; 95% CI: 0.81, 1.69; P = .41). Recursive partitioning analysis selected an ADC cutoff of 0.897 × 10-3 mm2/sec (P = .04) as a classifier for peripheral zone lesions with a PI-RADS score assessed on the ADC map (hereafter, ADC PI-RADS) of 3. The mDCE parameter did not differentiate ADC PI-RADS 3 lesions (P = .11), but classified lesions with ADC PI-RADS scores greater than 3 with low ADC values (less than 0.903 × 10-3 mm2/sec, P < .001) into groups with csPCa rates of 70% and 97% (P = .008). A lesion size cutoff of 1.5 cm and qualitative DCE parameters were not defined as classifiers according to recursive partitioning (P > .05). Conclusion Quantitative or qualitative dynamic contrast-enhanced MRI was not relevant for Prostate Imaging Reporting and Data System (PI-RADS) 3 lesion risk stratification, while quantitative apparent diffusion coefficient (ADC) values were helpful in upgrading PI-RADS 3 and PI-RADS 4 lesions. Quantitative ADC measurement may be more important for risk stratification than current methods in future versions of PI-RADS. © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Goh in this issue.

Application of a validated prostate MRI deep learning system to independent same-vendor multi-institutional data: demonstration of transferability.

OBJECTIVES: To evaluate a fully automatic deep learning system to detect and segment clinically significant prostate cancer (csPCa) on same-vendor prostate MRI from two different institutions not contributing to training of the system. MATERIALS AND METHODS: In this retrospective study, a previously bi-institutionally validated deep learning system (UNETM) was applied to bi-parametric prostate MRI data from one external institution (A), a PI-RADS distribution-matched internal cohort (B), and a csPCa stratified subset of single-institution external public challenge data (C). csPCa was defined as ISUP Grade Group ≥ 2 determined from combined targeted and extended systematic MRI/transrectal US-fusion biopsy. Performance of UNETM was evaluated by comparing ROC AUC and specificity at typical PI-RADS sensitivity levels. Lesion-level analysis between UNETM segmentations and radiologist-delineated segmentations was performed using Dice coefficient, free-response operating characteristic (FROC), and weighted alternative (waFROC). The influence of using different diffusion sequences was analyzed in cohort A. RESULTS: In 250/250/140 exams in cohorts A/B/C, differences in ROC AUC were insignificant with 0.80 (95% CI: 0.74-0.85)/0.87 (95% CI: 0.83-0.92)/0.82 (95% CI: 0.75-0.89). At sensitivities of 95% and 90%, UNETM achieved specificity of 30%/50% in A, 44%/71% in B, and 43%/49% in C, respectively. Dice coefficient of UNETM and radiologist-delineated lesions was 0.36 in A and 0.49 in B. The waFROC AUC was 0.67 (95% CI: 0.60-0.83) in A and 0.7 (95% CI: 0.64-0.78) in B. UNETM performed marginally better on readout-segmented than on single-shot echo-planar-imaging. CONCLUSION: For same-vendor examinations, deep learning provided comparable discrimination of csPCa and non-csPCa lesions and examinations between local and two independent external data sets, demonstrating the applicability of the system to institutions not participating in model training. CLINICAL RELEVANCE STATEMENT: A previously bi-institutionally validated fully automatic deep learning system maintained acceptable exam-level diagnostic performance in two independent external data sets, indicating the potential of deploying AI models without retraining or fine-tuning, and corroborating evidence that AI models extract a substantial amount of transferable domain knowledge about MRI-based prostate cancer assessment. KEY POINTS: • A previously bi-institutionally validated fully automatic deep learning system maintained acceptable exam-level diagnostic performance in two independent external data sets. • Lesion detection performance and segmentation congruence was similar on the institutional and an external data set, as measured by the weighted alternative FROC AUC and Dice coefficient. • Although the system generalized to two external institutions without re-training, achieving expected sensitivity and specificity levels using the deep learning system requires probability thresholds to be adjusted, underlining the importance of institution-specific calibration and quality control.

Ultra-High-b-Value Kurtosis Imaging for Noninvasive Tissue Characterization of Ovarian Lesions.

Background MRI with contrast material enhancement is the imaging modality of choice to evaluate sonographically indeterminate adnexal masses. The role of diffusion-weighted MRI, however, remains controversial. Purpose To evaluate the diagnostic performance of ultra-high-b-value diffusion kurtosis MRI in discriminating benign and malignant ovarian lesions. Materials and Methods This prospective cohort study evaluated consecutive women with sonographically indeterminate adnexal masses between November 2016 and December 2018. MRI at 3.0 T was performed, including diffusion-weighted MRI (b values of 0-2000 sec/mm2). Lesions were segmented on b of 1500 sec/mm2 by two readers in consensus and an additional independent reader by using full-lesion segmentations on a single transversal slice. Apparent diffusion coefficient (ADC) calculation and kurtosis fitting were performed. Differences in ADC, kurtosis-derived ADC (Dapp), and apparent kurtosis coefficient (Kapp) between malignant and benign lesions were assessed by using a logistic mixed model. Area under the receiver operating characteristic curve (AUC) for ADC, Dapp, and Kapp to discriminate malignant from benign lesions was calculated, as was specificity at a sensitivity level of 100%. Results from two independent reads were compared. Histopathologic analysis served as the reference standard. Results A total of 79 ovarian lesions in 58 women (mean age ± standard deviation, 48 years ± 14) were evaluated. Sixty-two (78%) lesions showed benign and 17 (22%) lesions showed malignant histologic findings. ADC and Dapp were lower and Kapp was higher in malignant lesions: median ADC, Dapp, and Kapp were 0.74 µm2/msec (range, 0.52-1.44 µm2/msec), 0.98 µm2/msec (range, 0.63-2.12 µm2/msec), and 1.01 (range, 0.69-1.30) for malignant lesions, and 1.13 µm2/msec (range, 0.35-2.63 µm2/msec), 1.45 µm2/msec (range, 0.44-3.34 µm2/msec), and 0.65 (range, 0.44-1.43) for benign lesions (P values of .01, .02, < .001, respectively). AUC for Kapp of 0.85 (95% confidence interval: 0.77, 0.94) was higher than was AUC from ADC of 0.78 (95% confidence interval: 0.67, 0.89; P = .047). Conclusion Diffusion-weighted MRI by using quantitative kurtosis variables is superior to apparent diffusion coefficient values in discriminating benign and malignant ovarian lesions and might be of future help in clinical practice, especially in patients with contraindication to contrast media application. © RSNA, 2020 Online supplemental material is available for this article.

Effects of arm truncation on the appearance of the halo artifact in 68Ga-PSMA-11 (HBED-CC) PET/MRI.

PURPOSE: PSMA ligand imaging with hybrid PET/MRI scanners could be an integral part of the clinical routine in the future. However, the first study about this novel method revealed a severe photopenic artifact ("halo artifact") around the urinary bladder causing significantly reduced tumor visibility. The aim of this evaluation was to analyze the role of arm truncation on the appearance of the halo artifact in 68Ga-PSMA-11 PET/MRI hypothesizing that this influences the appearance. METHODS: Twenty-seven consecutive patients were subjected to 68Ga-PSMA-11 PET/CT (1 h p.i.) followed by PET/MRI (3 h p.i.). PET/MRI was first started with scans of the abdomen to pelvis with arms positioned up above the head. Immediately thereafter, additional scans from the pelvis to abdomen were conducted with arms positioned down beside the trunk. All investigations were first analyzed separately and then compared with respect to tumor detection and tumor uptake (SUV) as well as the presence and intensity of the halo artifact. The Wilcoxon signed rank test was used to determine statistical differences including Bonferroni correction. RESULTS: The halo was significantly reduced if the arms were elevated. Lesions inside the halo artifact (n = 16) demonstrated significantly increased SUVmean (p = 0.0007) and SUVmax (p = 0.0024) with arms positioned up. The halo appearance and intensity was not dependent on the total activity and activity concentration of the urinary bladder. CONCLUSION: Positioning the arms down was shown to be significantly associated with the appearance of the halo artifact in PET/MRI. Positioning the arms up above the head can significantly reduce the halo artifact, thereby detecting more tumor lesions.

Clinical Workflow of Cone Beam Computer Tomography-Based Daily Online Adaptive Radiotherapy with Offline Magnetic Resonance Guidance: The Modular Adaptive Radiotherapy System (MARS).

PURPOSE: The Ethos (Varian Medical Systems) radiotherapy device combines semi-automated anatomy detection and plan generation for cone beam computer tomography (CBCT)-based daily online adaptive radiotherapy (oART). However, CBCT offers less soft tissue contrast than magnetic resonance imaging (MRI). This work aims to present the clinical workflow of CBCT-based oART with shuttle-based offline MR guidance. METHODS: From February to November 2023, 31 patients underwent radiotherapy on the Ethos (Varian, Palo Alto, CA, USA) system with machine learning (ML)-supported daily oART. Moreover, patients received weekly MRI in treatment position, which was utilized for daily plan adaptation, via a shuttle-based system. Initial and adapted treatment plans were generated using the Ethos treatment planning system. Patient clinical data, fractional session times (MRI + shuttle transport + positioning, adaptation, QA, RT delivery) and plan selection were assessed for all fractions in all patients. RESULTS: In total, 737 oART fractions were applied and 118 MRIs for offline MR guidance were acquired. Primary sites of tumors were prostate (n = 16), lung (n = 7), cervix (n = 5), bladder (n = 1) and endometrium (n = 2). The treatment was completed in all patients. The median MRI acquisition time including shuttle transport and positioning to initiation of the Ethos adaptive session was 53.6 min (IQR 46.5-63.4). The median total treatment time without MRI was 30.7 min (IQR 24.7-39.2). Separately, median adaptation, plan QA and RT times were 24.3 min (IQR 18.6-32.2), 0.4 min (IQR 0.3-1,0) and 5.3 min (IQR 4.5-6.7), respectively. The adapted plan was chosen over the scheduled plan in 97.7% of cases. CONCLUSION: This study describes the first workflow to date of a CBCT-based oART combined with a shuttle-based offline approach for MR guidance. The oART duration times reported resemble the range shown by previous publications for first clinical experiences with the Ethos system.

Test-retest, inter- and intra-rater reproducibility of size measurements of focal bone marrow lesions in MRI in patients with multiple myeloma.

OBJECTIVE: To investigate the reproducibility of size measurements of focal bone marrow lesions (FL) in MRI in patients with monoclonal plasma cell disorders under variation of patient positioning and observer. METHODS: A data set from a prospective test-retest study was used, in which 37 patients with a total of 140 FL had undergone 2 MRI scans with identical parameters after patient repositioning. Two readers measured long and short axis diameter on the initial scan in T1 weighted, T2 weighted short tau inversion recovery and diffusion-weighted imaging sequences. The first reader additionally measured FL on the retest-scan. The Bland-Altman method was used to assess limits of agreement (LoA), and the frequencies of absolute size changes were calculated. RESULTS: In the simple test-retest experiment with one identical reader, a deviation of ≥1 mm / ≥2 mm / ≥3 mm for the long axis diameter in T1 weighted images was observed in 66% / 25% / 8% of cases. When comparing measurements of one reader on the first scan to the measurement of the other reader on the retest scan, a change of ≥1 mm / ≥3 mm / ≥5 mm for the long axis diameter in T1 weighted images was observed in 78% / 21% / 5% of cases. CONCLUSION: Small deviations in FL size are common and probably due to variation in patient positioning or inter-rater variability alone, without any actual biological change of the FL. Knowledge of the uncertainty associated with size measurements of FLs is critical for radiologists and oncologists when interpreting changes in FL size in clinical practice and in clinical trials. ADVANCES IN KNOWLEDGE: According to the MY-RADs criteria, size measurements of focal lesions in MRI are now of relevance for response assessment in patients with monoclonal plasma cell disorders.Size changes of 1 or 2 mm are frequently observed due to uncertainty of the measurement only, while the actual focal lesion has not undergone any biological change.Size changes of at least 6 mm or more in T1 weighted or T2 weighted short tau inversion recovery sequences occur in only 5% or less of cases when the focal lesion has not undergone any biological change.

In Vivo Repeatability and Multiscanner Reproducibility of MRI Radiomics Features in Patients With Monoclonal Plasma Cell Disorders: A Prospective Bi-institutional Study.

OBJECTIVES: Despite the extensive number of publications in the field of radiomics, radiomics algorithms barely enter large-scale clinical application. Supposedly, the low external generalizability of radiomics models is one of the main reasons, which hinders the translation from research to clinical application. The objectives of this study were to investigate reproducibility of radiomics features (RFs) in vivo under variation of patient positioning, magnetic resonance imaging (MRI) sequence, and MRI scanners, and to identify a subgroup of RFs that shows acceptable reproducibility across all different acquisition scenarios. MATERIALS AND METHODS: Between November 30, 2020 and February 16, 2021, 55 patients with monoclonal plasma cell disorders were included in this prospective, bi-institutional, single-vendor study. Participants underwent one reference scan at a 1.5 T MRI scanner and several retest scans: once after simple repositioning, once with a second MRI protocol, once at another 1.5 T scanner, and once at a 3 T scanner. Radiomics feature from the bone marrow of the left hip bone were extracted, both from original scans and after different image normalizations. Intraclass correlation coefficient (ICC) was used to assess RF repeatability and reproducibility. RESULTS: Fifty-five participants (mean age, 59 ± 7 years; 36 men) were enrolled. For T1-weighted images after muscle normalization, in the simple test-retest experiment, 110 (37%) of 295 RFs showed an ICC ≥0.8: 54 (61%) of 89 first-order features (FOFs), 35 (95%) of 37 volume and shape features, and 21 (12%) of 169 texture features (TFs). When the retest was performed with different technical settings, even after muscle normalization, the number of FOF/TF with an ICC ≥0.8 declined to 58/13 for the second protocol, 29/7 for the second 1.5 T scanner, and 49/7 for the 3 T scanner, respectively. Twenty-five (28%) of the 89 FOFs and 6 (4%) of the 169 TFs from muscle-normalized T1-weighted images showed an ICC ≥0.8 throughout all repeatability and reproducibility experiments. CONCLUSIONS: In vivo, only few RFs are reproducible with different MRI sequences or different MRI scanners, even after application of a simple image normalization. Radiomics features selected by a repeatability experiment only are not necessarily suited to build radiomics models for multicenter clinical application. This study isolated a subset of RFs, which are robust to variations in MRI acquisition observed in scanners from 1 vendor, and therefore are candidates to build reproducible radiomics models for monoclonal plasma cell disorders for multicentric applications, at least when centers are equipped with scanners from this vendor.

Addressing image misalignments in multi-parametric prostate MRI for enhanced computer-aided diagnosis of prostate cancer.

Prostate cancer (PCa) diagnosis on multi-parametric magnetic resonance images (MRI) requires radiologists with a high level of expertise. Misalignments between the MRI sequences can be caused by patient movement, elastic soft-tissue deformations, and imaging artifacts. They further increase the complexity of the task prompting radiologists to interpret the images. Recently, computer-aided diagnosis (CAD) tools have demonstrated potential for PCa diagnosis typically relying on complex co-registration of the input modalities. However, there is no consensus among research groups on whether CAD systems profit from using registration. Furthermore, alternative strategies to handle multi-modal misalignments have not been explored so far. Our study introduces and compares different strategies to cope with image misalignments and evaluates them regarding to their direct effect on diagnostic accuracy of PCa. In addition to established registration algorithms, we propose 'misalignment augmentation' as a concept to increase CAD robustness. As the results demonstrate, misalignment augmentations can not only compensate for a complete lack of registration, but if used in conjunction with registration, also improve the overall performance on an independent test set.

Reattachable fiducial skin marker for automatic multimodality registration.

PURPOSE: Fusing image information has become increasingly important for optimal diagnosis and treatment of the patient. Despite intensive research towards markerless registration approaches, fiducial marker-based methods remain the default choice for a wide range of applications in clinical practice. However, as especially non-invasive markers cannot be positioned reproducibly in the same pose on the patient, pre-interventional imaging has to be performed immediately before the intervention for fiducial marker-based registrations. METHODS: We propose a new non-invasive, reattachable fiducial skin marker concept for multi-modal registration approaches including the use of electromagnetic or optical tracking technologies. We furthermore describe a robust, automatic fiducial marker localization algorithm for computed tomography (CT) and magnetic resonance imaging (MRI) images. Localization of the new fiducial marker has been assessed for different marker configurations using both CT and MRI. Furthermore, we applied the marker in an abdominal phantom study. For this, we attached the marker at three poses to the phantom, registered ten segmented targets of the phantom's CT image to live ultrasound images and determined the target registration error (TRE) for each target and each marker pose. RESULTS: Reattachment of the marker was possible with a mean precision of 0.02 mm ± 0.01 mm. Our algorithm successfully localized the marker automatically in all ([Formula: see text]) evaluated CT/MRI images. Depending on the marker pose, the mean ([Formula: see text]) TRE of the abdominal phantom study ranged from 1.51 ± 0.75 mm to 4.65 ± 1.22 mm. CONCLUSIONS: The non-invasive, reattachable skin marker concept allows reproducible positioning of the marker and automatic localization in different imaging modalities. The low TREs indicate the potential applicability of the marker concept for clinical interventions, such as the puncture of abdominal lesions, where current image-based registration approaches still lack robustness and existing marker-based methods are often impractical.

Pancreatic imaging using diffusivity mapping - Influence of sequence technique on qualitative and quantitative analysis.

PURPOSE: To compare image quality of an optimized diffusion weighted imaging (DWI) sequence with advanced post-processing and motion correction (advanced-EPI) to a standard DWI protocol (standard-EPI) in pancreatic imaging. MATERIALS AND METHODS: 62 consecutive patients underwent abdominal MRI at 1.5 T were included in this retrospective analysis of data collected as part of an IRB approved study. All patients received a standard-EPI and an advanced-EPI DWI with advanced post-processing and motion correction. Two blinded radiologists evaluated the parameters image quality, detail of parenchyma, sharpness of boundaries and discernibility from adjacent structures on b = 900 s/mm2 images using a Likert-like scale. Segmentation of pancreatic head, body and tail were obtained and apparent diffusion coefficient (ADC) was calculated separately for each region. Apparent tissue-to-background ratio (TBR) was calculated at b = 50 s/mm2 and at b = 900 s/mm2. RESULTS: The advanced-EPI yielded significantly higher scores for pancreatic parameters of image quality, detail level of parenchyma, sharpness of boundaries and discernibility from adjacent structures in comparison to standard-EPI (p < 0.001 for all, kappa = [0.46,0.71]) and was preferred in 96% of the cases when directly compared. ADC of the pancreas was 7% lower in advanced-EPI (1.236 ± 0.152 vs. 1.146 ± 0.126 µm2/ms, p < 0.001). ADC in the pancreatic tail was significantly lower for both sequences compared to head and body (all p < 0.001). There was comparable TBR for both sequences at b = 50 s/mm2 (standard-EPI: 19.0 ± 5.9 vs. advanced-EPI: 19.0 ± 6.4, p = 0.96), whereas at b = 900 s/mm2, TBR was 51% higher for advanced-EPI (standard-EPI: 7.1 ± 2.5 vs. advanced-EPI: 10.8 ± 5.1, p < 0.001). CONCLUSION: An advanced DWI sequence might increase image quality for focused imaging of the pancreas and providing improved parenchymal detail levels compared to a standard DWI.

An abdominal phantom with anthropomorphic organ motion and multimodal imaging contrast for MR-guided radiotherapy.

Purpose. Improvements in image-guided radiotherapy (IGRT) enable accurate and precise treatment of moving tumors in the abdomen while simultaneously sparing healthy tissue. However, the lack of validation tools for newly developed MR-guided radiotherapy hybrid devices such as the MR-Linac is an open issue. This study presents a custom developed abdominal phantom with respiratory organ motion and multimodal imaging contrast to perform end-to-end tests for IGRT treatment planning scenarios.Methods. The abdominal phantom contains deformable and anatomically shaped liver and kidney models made of Ni-DTPA and KCl-doped agarose mixtures that can be reproducibly positioned within the phantom. Organ models are wrapped in foil to avoid ion exchange with the surrounding agarose and to provide stable T1 and T2 relaxation times as well as HU numbers. Breathing motion is realized by a diaphragm connected to an actuator that is hydraulically controlled via a programmable logic controller. With this system, artificial and patient-specific breathing patterns can be carried out. In 1.5 T magnetic resonance imaging (MRI), diaphragm, liver and kidney motion was measured and compared to the breathing motion of a healthy male volunteer for different breathing amplitudes including shallow, normal and deep breathing.Results. The constructed abdominal phantom demonstrated organ-equivalent intensity values in CT as well as in MRI. T1-weighted (T1w) and T2-weighted (T2w) relaxation times for 1.5 T and CT numbers were 552.9 ms, 48.2 ms and 48.8 HU (liver) as well as 950.42 ms, 79 ms and 28.2 HU (kidney), respectively. These values were stable for more than six months. Extracted breathing motion from a healthy volunteer revealed a liver to diaphragm motion ratio (LDMR) of 64.4% and a kidney to diaphragm motion ratio (KDMR) of 30.7%. Well-comparable values were obtained for the phantom (LDMR: 65.5%, KDMR: 27.5%).Conclusions. The abdominal phantom demonstrated anthropomorphic T1 and T2 relaxation times as well as HU numbers and physiological motion pattern in MRI and CT. This allows for wide use in the validation of IGRT including MRgRT.

Repeatability and Reproducibility of ADC Measurements and MRI Signal Intensity Measurements of Bone Marrow in Monoclonal Plasma Cell Disorders: A Prospective Bi-institutional Multiscanner, Multiprotocol Study.

BACKGROUND/OBJECTIVES: Apparent diffusion coefficient (ADC) and signal intensity (SI) measurements play an increasing role in magnetic resonance imaging (MRI) of monoclonal plasma cell disorders. The purpose of this study was to assess interrater variability, repeatability, and reproducibility of ADC and SI measurements from bone marrow (BM) under variation of MRI protocols and scanners. PATIENTS AND METHODS: Fifty-five patients with suspected or confirmed monoclonal plasma cell disorder were prospectively included in this institutional review board-approved study and underwent several measurements after the standard clinical whole-body MR scan, including repeated scan after repositioning, scan with a second MRI protocol, scan at a second 1.5 T scanner with a harmonized MRI protocol, and scan at a 3 T scanner. For T1-weighted, T2-weighted STIR, B800 images, and ADC maps, regions of interest were placed in the BM of the iliac crest and sacral bone, and in muscle tissue for image normalization. Bland-Altman plots were constructed, and absolute bias, relative bias to mean, limits of agreement, and coefficients of variation were calculated. RESULTS: Interrater variability and repeatability experiments showed a maximal relative bias of -0.077 and a maximal coefficient of variation of 16.2% for all sequences. Although the deviations at the second 1.5 T scanner with harmonized MRI protocol to the first 1.5 T scanner showed a maximal relative bias of 0.124 for all sequences, the variation of the MRI protocol and scan at the 3 T scanner led to large relative biases of up to -0.357 and -0.526, respectively. When comparing the 3 T scanner to the 1.5 T scanner, normalization to muscle reduced the bias of T1-weighted and T2-weighted sequences, but not of ADC maps. CONCLUSIONS: The MRI scanners with identical field strength and harmonized MRI protocols can provide relatively stable quantitative measurements of BM ADC and SI. Deviations in MRI field strength and MRI protocol should be avoided when applying ADC cutoff values, which were established at other scanners or when performing multicentric imaging trials.

Adapting Imaging Protocols for PET-CT and PET-MRI for Immunotherapy Monitoring.

Hybrid imaging with positron emission tomography (PET) in combination with computer tomography (CT) is a well-established diagnostic tool in oncological staging and restaging. The combination of PET with magnetic resonance imaging (MRI) as a clinical scanner was introduced approximately 10 years ago. Although MRI provides superb soft tissue contrast and functional information without the radiation exposure of CT, PET-MRI is not as widely introduced in oncologic imaging as PET-CT. One reason for this hesitancy lies in the relatively long acquisition times for a PET-MRI scan, if the full diagnostic potential of MRI is exploited. In this review, we discuss the possible advantages of combined imaging protocols of PET-CT and PET-MRI, within the context of staging and restaging of patients under immunotherapy, in order to achieve "multi-hybrid imaging" in one single patient visit.

Comparison of single-scanner single-protocol quantitative ADC measurements to ADC ratios to detect clinically significant prostate cancer.

BACKGROUND: Mean ADC has high predictive value for the presence of clinically significant prostate cancer (sPC). Measurement variability is introduced by different scanners, protocols, intra-and inter-patient variation. Internal calibration by ADC ratios can address such fluctuations however can potentially lower the biological value of quantitative ADC determination by being sensitive to deviations in reference tissue signal. PURPOSE: To better understand the predictive value of quantitative ADC measurements in comparison to internal reference ratios when measured in a single scanner, single protocol setup. MATERIALS AND METHODS: 284 consecutive patients who underwent 3 T MRI on a single scanner followed by MRI-transrectal ultrasound fusion biopsy were included. A board-certified radiologist retrospectively reviewed all MRIs blinded to clinical information and placed regions of interest (ROI) on all focal lesions and the following reference regions: normal-appearing peripheral zone (PZNL) and transition zone (TZNL), the urinary bladder (BLA), and right and left internal obturator muscle (RIOM, LIOM). ROI-based mean ADC and ADC ratios to the reference regions were compared regarding their ability to predict the aggressiveness of prostate cancer. Spearman's rank correlation coefficient was used to estimate the correlation between ADC parameters, Gleason score (GS) and ADC ratios. The primary endpoint was presence of sPC, defined as a GS ≥ 3 + 4. Univariable and multivariable logistic regression models were constructed to predict sPC. Receiver operating characteristics curves (ROC) were used for visualization; DeLong test was used to evaluate the differences of the area under the curve (AUC). Bias-corrected AUC values and corresponding 95 %-CI were calculated using bootstrapping with 100 bootstrap samples. RESULTS: After exclusion of patients who received prior treatment, 259 patients were included in the final cohort of which 220 harbored 351 MR lesions. Mean ADC and ADC ratios demonstrated a negative correlation with the GS. Mean ADC had the strongest correlation with ρ of -0.34, followed by ADCratioPZNL (ρ=-0.32). All ADC parameters except ADCratioLIOM (p = 0.07) were associated with sPC p<0.05). Mean ADC and ADCratioPZNL had the highest ROC AUC of all parameters (0.68). Multivariable models with mean ADC improve predictive performance. CONCLUSIONS: A highly standardized single-scanner mean ADC measurement could not be improved upon using any of the single ADC ratio parameters or combinations of these parameters in predicting the aggressiveness of prostate cancer.

Fully Automatic Deep Learning in Bi-institutional Prostate Magnetic Resonance Imaging: Effects of Cohort Size and Heterogeneity.

BACKGROUND: The potential of deep learning to support radiologist prostate magnetic resonance imaging (MRI) interpretation has been demonstrated. PURPOSE: The aim of this study was to evaluate the effects of increased and diversified training data (TD) on deep learning performance for detection and segmentation of clinically significant prostate cancer-suspicious lesions. MATERIALS AND METHODS: In this retrospective study, biparametric (T2-weighted and diffusion-weighted) prostate MRI acquired with multiple 1.5-T and 3.0-T MRI scanners in consecutive men was used for training and testing of prostate segmentation and lesion detection networks. Ground truth was the combination of targeted and extended systematic MRI-transrectal ultrasound fusion biopsies, with significant prostate cancer defined as International Society of Urological Pathology grade group greater than or equal to 2. U-Nets were internally validated on full, reduced, and PROSTATEx-enhanced training sets and subsequently externally validated on the institutional test set and the PROSTATEx test set. U-Net segmentation was calibrated to clinically desired levels in cross-validation, and test performance was subsequently compared using sensitivities, specificities, predictive values, and Dice coefficient. RESULTS: One thousand four hundred eighty-eight institutional examinations (median age, 64 years; interquartile range, 58-70 years) were temporally split into training (2014-2017, 806 examinations, supplemented by 204 PROSTATEx examinations) and test (2018-2020, 682 examinations) sets. In the test set, Prostate Imaging-Reporting and Data System (PI-RADS) cutoffs greater than or equal to 3 and greater than or equal to 4 on a per-patient basis had sensitivity of 97% (241/249) and 90% (223/249) at specificity of 19% (82/433) and 56% (242/433), respectively. The full U-Net had corresponding sensitivity of 97% (241/249) and 88% (219/249) with specificity of 20% (86/433) and 59% (254/433), not statistically different from PI-RADS (P > 0.3 for all comparisons). U-Net trained using a reduced set of 171 consecutive examinations achieved inferior performance (P < 0.001). PROSTATEx training enhancement did not improve performance. Dice coefficients were 0.90 for prostate and 0.42/0.53 for MRI lesion segmentation at PI-RADS category 3/4 equivalents. CONCLUSIONS: In a large institutional test set, U-Net confirms similar performance to clinical PI-RADS assessment and benefits from more TD, with neither institutional nor PROSTATEx performance improved by adding multiscanner or bi-institutional TD.

Advanced Diffusion-Weighted Abdominal Imaging: Qualitative and Quantitative Comparison of High and Ultra-High b-Values for Lesion Detection and Image Quality.

INTRODUCTION: Magnetic resonance imaging (MRI) of the abdomen increasingly incorporates diffusion-weighted imaging (DWI) sequences. Whereas DWI can substantially aid in detecting and characterizing suspicious findings, it remains unclear to what extent the use of ultra-high b-value DWI might further be of aid for the radiologist especially when using DWI sequences with advanced processing. The target of this study was therefore to compare high and ultra-high b-value DWI in abdominal MRI examinations. METHODS: This institutional review board-approved, prospective study included abdominal MRI examinations of 70 oncologic patients (mean age, 58 years; range, 21-90 years) examined with a clinical 1.5 T MRI scanner (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) with an advanced echo planar DWI sequence (b = 0, 50, 900, and 1500 s/mm) after ex vivo phantom and in vivo volunteer investigations. High b900 and ultra-high b1500 DWIs were compared by a qualitative reading for image quality and lesion conspicuity using a 5-point Likert scale with 2 radiologists as readers. The ratios of apparent signal intensities of suspicious lesions/normal tissue of the same organ (LNTRs) were calculated. Appropriate methods were used for statistical analysis, including Wilcoxon signed-rank test and κ statistic for interreader agreement analysis (P < 0.05/0.0125/0.005 after Bonferroni correction). RESULTS: Image quality was significantly increased with b900 as compared with b1500 DWI (P < 0.001) despite using an advanced DWI sequence. A total of 153 suspicious lesions were analyzed. Overall reader confidence for characterization/detection of malignant lesions and, correspondingly, the LNTR (mean, 2.7 ± 1.8 vs 2.4 ± 1.6) were significantly higher with b900 than with b1500 DWI (P < 0.001 and P < 0.001). The increased confidence of lesion recognition and LNTR in the b900 DWI remained significant qualitatively in lymphatic and hepatic lesions and quantitatively in lymphatic, pulmonal, and osseous lesions. CONCLUSIONS: Using high b-value DWI (900 s/mm) provided an improved image quality and also lesion conspicuity as compared with ultra-high b-value DWI (1500 s/mm) in oncologic abdominal examinations despite using advanced processing. Consequently, the value for additional ultra-high b-value DWI in oncologic examinations should be critically evaluated in future studies.

Modulating Diffusion-Weighted Magnetic Resonance Imaging for Screening in Oncologic Tertiary Prevention: A Prospective Ex Vivo and In Vivo Study.

INTRODUCTION: Diffusion-weighted imaging (DWI) is an important part of oncological magnetic resonance imaging (MRI) examinations, especially for tertiary cancer prevention in terms of early detection of recurrent disease. However, abdominal studies can be challenged by motion artifacts, poor signal-to-noise ratios, and visibility of retroperitoneal structures, which necessitates sequence optimization depending on the investigated region. This study aims at prospectively evaluating an adapted DWI sequence ex vivo and in vivo in oncologic patients undergoing abdominal MRI. METHODS: This institutional review board-approved, prospective study included phantom measurements, volunteer examinations, and oncologic patient examinations of the abdomen. Fifty-seven MRI examinations in 54 patients (mean age, 58 years; range, 21-90 years) were included into the analysis. The MRI examination were performed at a 1.5 T MRI scanner (MAGNETOM Aera; Siemens Healthcare, Erlangen, Germany) and included both a standard EPI-DWI (s-DWI; b = 50, 900 s/mm) and an adapted DWI (opt-DWI; EPI-DWI with b = 0, 50, 900, 1500 s/mm, acquisition with higher spatial resolution and optimized processing for the abdomen including motion correction, adaptive image combination, and background suppression). For b = 900 s/mm, the ratio of signal intensity in the normal tissue and the standard deviation of the noise in the surrounding air was quantitatively calculated; image quality and tissue differentiation parameters were rated by 2 independent, blinded readers using a 5-point Likert scale. Statistics included Wilcoxon signed-rank test and kappa statistic (P < 0.05/0.0125 after Bonferroni correction). RESULTS: The DWI phantom demonstrated an optimized contour sharpness and inlay differentiation for opt-DWI. The apparent ratio of normal tissue signal/standard deviation of background noise at b = 900 s/mm of the right/left hemiabdomen was significantly increased in opt-DWI (mean, 71.9 ± 23.5/86.0 ± 43.3) versus s-DWI (mean, 51.4 ± 15.4/63.4 ± 36.5; P < 0.001). Image quality parameters (contour sharpness and tissue differentiation of upper abdominal and retroperitoneal structures) were significantly increased in opt-DWI versus s-DWI (P < 0.001). Interreader reliability test showed good agreement (kappa = 0.768; P < 0.001). DISCUSSION: This study prospectively evaluated the potential of adapted DWI for screening in tertiary prevention of oncologic patients. An optimized DWI protocol with advanced processing achieved improved image quality in quantitative and qualitative analyses. Oncological optimization of DWI should be performed before its application in cancer patients to improve both screening and follow-up examinations, to better unleash the diagnostic potential of DWI.

Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted.

BACKGROUND: The "glymphatic system" (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies a pathway through and out of the central nervous system (CNS); malfunction of the system is implicated in a variety of neurological disorders. In this exploratory study, we analyzed the potential of a new imaging approach that we coined delayed T2-weighted gadolinium-enhanced imaging to visualize the GS in vivo. METHODS: Heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) magnetic resonance imaging was obtained before, and 3 hours and 24 hours after intravenous gadolinium-based contrast agent (GBCA) application in 33 neurologically healthy patients and 7 patients with an impaired blood-brain barrier (BBB) due to cerebral metastases. Signal intensity (SI) was determined in various cerebral fluid spaces, and white matter hyperintensities were quantified by applying the Fazekas scoring system. FINDINGS: Delayed hT2w-FLAIR showed GBCA entry into the CNS via the choroid plexus and the ciliary body, with GBCA drainage along perineural sheaths of cranial nerves and along perivascular spaces of penetrating cortical arteries. In all patients and all sites, a significant SI increase was found for the 3 hours and 24 hours time points compared with baseline. Although no significant difference in SI was found between neurologically healthy patients and patients with an impaired BBB, a significant positive correlation between Fazekas scoring system and SI increase in the perivascular spaces 3 hours post injection was shown. INTERPRETATION: Delayed T2-weighted gadolinium-enhanced imaging can visualize the GBCA pathway into and through the GS. Presence of GBCAs within the GS might be regarded as part of the natural excretion process and should not be mixed up with gadolinium deposition. Rather, the correlation found between deep white matter hyperintensities, an imaging sign of vascular dementia, and GS functioning demonstrated feasibility to exploit the pathway of GBCAs through the GS for diagnostic purposes.

4D dose calculation for pencil beam scanning proton therapy of pancreatic cancer using repeated 4DMRI datasets.

4D magnetic resonance imaging (4DMRI) has a high potential for pancreatic cancer treatments using proton therapy, by providing time-resolved volumetric images with a high soft-tissue contrast without exposing the patient to any additional imaging dose. In this study, we aim to show the feasibility of 4D treatment planning for pencil beam scanning (PBS) proton therapy of pancreatic cancer, based on five repeated 4DMRI datasets and 4D dose calculations (4DDC) for one pancreatic cancer patient. To investigate the dosimetric impacts of organ motion, deformation vector fields were extracted from 4DMRI, which were then used to warp a static CT of the patient, so as to generate synthetic 4DCT (4DCT-MRI). CTV motion amplitudes <15 mm were observed for this patient. The results from 4DDC show pronounced interplay effects in the CTV with dose homogeneity d5/d95 and dose coverage v95 being 1.14 and 91%, respectively, after a single fraction of the treatment. An averaging effect was further observed when increasing the number of fractions. Motion effects can become less dominant and dose homogeneity d5/d95 = 1.03 and dose coverage v95 = [Formula: see text] within the CTV can be achieved after 28 fractions. The observed inter-fractional organ and tumor motion variations underline the importance of 4D imaging before and during PBS proton therapy.

Comparison of 68Ga-DOTATOC-PET/CT and PET/MRI hybrid systems in patients with cranial meningioma: Initial results.

BACKGROUND: (68)Ga-DOTATOC-PET/CT is a well-established method for detecting and targeting the volume definition of meningiomas prior to radiotherapy. Moreover, there is evidence that this method is able to detect meningiomas with higher sensitivity than the goldstandard MRI. Since the hybrid PET/MRI scanner became available in the past few years, the next stage of development could consequently evolve by evaluating the feasibility of a hybrid PET/MRI scanner using (68)Ga-DOTATOC for detecting meningiomas. METHODS: Fifteen patients received (68)Ga-DOTATOC-PET/CT (0.5 h post injection [p.i.]) followed by PET/MRI 2 hours p.i. Both investigations were analyzed separately and then compared with respect to image quality, detection of intracranial meningiomas, and radiotracer uptake values (RUVs). In addition, ratios between radiotracer uptake in meningiomas and pituitary glands were compared between both PET/CT and PET/MRI. RESULTS: Overall, 33 intracranial meningiomas were detected. All were visible with high contrast in both PET/CT and PET/MRI. (68)Ga-DOTATOC-PET/MRI provided flawless image quality without artefacts. Calculated RUV in meningiomas, as well as the ratios of RUVs in meningiomas to those of pituitary glands, were higher in PET/CT. As a result, meningiomas can be distinguished from pituitary glands better in early images. CONCLUSIONS: (68)Ga-DOTATOC-PET/MRI provided flawless image quality and presented an ideal combination of high sensitivity/specificity (PET) and the best possible morphological visualization of meningiomas (MRI). In addition, excellent detection of meningiomas is already possible at 0.5 hours p.i. Later images do not improve the distinction between pituitary gland and adjacent meningiomas. However, RUVs need to be carefully compared between both imaging modalities.