Discrimination Between Benign and Malignant Lesions With Restriction Spectrum Imaging MRI in an Enriched Breast Cancer Screening Cohort.

BACKGROUND: Breast cancer screening with dynamic contrast-enhanced MRI (DCE-MRI) is recommended for high-risk women but has limitations, including variable specificity and difficulty in distinguishing cancerous (CL) and high-risk benign lesions (HRBL) from average-risk benign lesions (ARBL). Complementary non-invasive imaging techniques would be useful to improve specificity. PURPOSE: To evaluate the performance of a previously-developed breast-specific diffusion-weighted MRI (DW-MRI) model (BS-RSI3C) to improve discrimination between CL, HRBL, and ARBL in an enriched screening population. STUDY TYPE: Prospective. SUBJECTS: Exactly 187 women, either with mammography screening recommending additional imaging (N = 49) or high-risk individuals undergoing routine breast MRI (N = 138), before the biopsy. FIELD STRENGTH/SEQUENCE: Multishell DW-MRI echo planar imaging sequence with a reduced field of view at 3.0 T. ASSESSMENT: A total of 72 women had at least one biopsied lesion, with 89 lesions categorized into ARBL, HRBL, CL, and combined CLs and HRBLs (CHRLs). DW-MRI data were processed to produce apparent diffusion coefficient (ADC) maps, and estimate signal contributions (C1, C2, and C3-restricted, hindered, and free diffusion, respectively) from the BS-RSI3C model. Lesion regions of interest (ROIs) were delineated on DW images based on suspicious DCE-MRI findings by two radiologists; control ROIs were drawn in the contralateral breast. STATISTICAL TESTS: One-way ANOVA and two-sided t-tests were used to assess differences in signal contributions and ADC values among groups. P-values were adjusted using the Bonferroni method for multiple testing, P = 0.05 was used for the significance level. Receiver operating characteristics (ROC) curves and intra-class correlations (ICC) were also evaluated. RESULTS: C1, √C1C2, and log C 1 C 2 C 3 $$ \log \left(\frac{{\mathrm{C}}_1{\mathrm{C}}_2}{{\mathrm{C}}_3}\right) $$ were significantly different in HRBLs compared with ARBLs (P-values < 0.05). The log C 1 C 2 C 3 $$ \log \left(\frac{{\mathrm{C}}_1{\mathrm{C}}_2}{{\mathrm{C}}_3}\right) $$ had the highest AUC (0.821) in differentiating CHRLs from ARBLs, performing better than ADC (0.696), especially in non-mass enhancement (0.776 vs. 0.517). DATA CONCLUSION: This study demonstrated the BS-RSI3C could differentiate HRBLs from ARBLs in a screening population, and separate CHRLs from ARBLs better than ADC. TECHNICAL EFFICACY STAGE: 2.

Quantitative MRI biomarker for classification of clinically significant prostate cancer: Calibration for reproducibility across echo times.

PURPOSE: The purpose of the present study is to develop a calibration method to account for differences in echo times (TE) and facilitate the use of restriction spectrum imaging restriction score (RSIrs) as a quantitative biomarker for the detection of clinically significant prostate cancer (csPCa). METHODS: This study included 197 consecutive patients who underwent MRI and biopsy examination; 97 were diagnosed with csPCa (grade group ≥ 2). RSI data were acquired three times during the same session: twice at minimum TE ~75 ms and once at TE = 90 ms (TEmin1, TEmin2, and TE90, respectively). A linear regression model was determined to match the C-maps of TE90 to the reference C-maps of TEmin1 within the interval ranging from 95th to 99th percentile of signal intensity within the prostate. RSIrs comparisons were made at the 98th percentile within each patient's prostate. We compared RSIrs from calibrated TE90 (RSIrsTE90corr) and uncorrected TE90 (RSIrsTE90) to RSIrs from reference TEmin1 (RSIrsTEmin1) and repeated TEmin2 (RSIrsTEmin2). Calibration performance was evaluated with sensitivity, specificity and area under the ROC curve (AUC). RESULTS: Scaling factors for C1, C2, C3, and C4 were estimated as 1.68, 1.33, 1.02, and 1.13, respectively. In non-csPCa cases, the 98th percentile of RSIrsTEmin2 and RSIrsTEmin1 differed by 0.27 ± 0.86SI (mean ± standard deviation), whereas RSIrsTE90 differed from RSIrsTEmin1 by 1.82 ± 1.20SI. After calibration, this bias was reduced to -0.51 ± 1.21SI, representing a 72% reduction in absolute error. For patients with csPCa, the difference was 0.54 ± 1.98SI between RSIrsTEmin2 and RSIrsTEmin1 and 2.28 ± 2.06SI between RSIrsTE90 and RSIrsTEmin1. After calibration, the mean difference decreased to -1.03SI, a 55% reduction in absolute error. At the Youden index for patient-level classification of csPCa (8.94SI), RSIrsTEmin1 has a sensitivity of 66% and a specificity of 72%. CONCLUSIONS: The proposed linear calibration method produces similar quantitative biomarker values for acquisitions with different TE, reducing TE-induced error by 72% and 55% for non-csPCa and csPCa, respectively.

Characterization of the diffusion signal of breast tissues using multi-exponential models.

PURPOSE: Restriction spectrum imaging (RSI) decomposes the diffusion-weighted MRI signal into separate components of known apparent diffusion coefficients (ADCs). The number of diffusion components and optimal ADCs for RSI are organ-specific and determined empirically. The purpose of this work was to determine the RSI model for breast tissues. METHODS: The diffusion-weighted MRI signal was described using a linear combination of multiple exponential components. A set of ADC values was estimated to fit voxels in cancer and control ROIs. Later, the signal contributions of each diffusion component were estimated using these fixed ADC values. Relative-fitting residuals and Bayesian information criterion were assessed. Contrast-to-noise ratio between cancer and fibroglandular tissue in RSI-derived signal contribution maps was compared to DCE imaging. RESULTS: A total of 74 women with breast cancer were scanned at 3.0 Tesla MRI. The fitting residuals of conventional ADC and Bayesian information criterion suggest that a 3-component model improves the characterization of the diffusion signal over a biexponential model. Estimated ADCs of triexponential model were D1,3 = 0, D2,3 = 1.5 × 10-3 , and D3,3 = 10.8 × 10-3 mm2 /s. The RSI-derived signal contributions of the slower diffusion components were larger in tumors than in fibroglandular tissues. Further, the contrast-to-noise and specificity at 80% sensitivity of DCE and a subset of RSI-derived maps were equivalent. CONCLUSION: Breast diffusion-weighted MRI signal was best described using a triexponential model. Tumor conspicuity in breast RSI model is comparable to that of DCE without the use of exogenous contrast. These data may be used as differential features between healthy and malignant breast tissues.

Voxel-level Classification of Prostate Cancer on Magnetic Resonance Imaging: Improving Accuracy Using Four-Compartment Restriction Spectrum Imaging.

BACKGROUND: Diffusion magnetic resonance imaging (MRI) is integral to detection of prostate cancer (PCa), but conventional apparent diffusion coefficient (ADC) cannot capture the complexity of prostate tissues and tends to yield noisy images that do not distinctly highlight cancer. A four-compartment restriction spectrum imaging (RSI4 ) model was recently found to optimally characterize pelvic diffusion signals, and the model coefficient for the slowest diffusion compartment, RSI4 -C1 , yielded greatest tumor conspicuity. PURPOSE: To evaluate the slowest diffusion compartment of a four-compartment spectrum imaging model (RSI4 -C1 ) as a quantitative voxel-level classifier of PCa. STUDY TYPE: Retrospective. SUBJECTS: Forty-six men who underwent an extended MRI acquisition protocol for suspected PCa. Twenty-three men had benign prostates, and the other 23 men had PCa. FIELD STRENGTH/SEQUENCE: A 3 T, multishell diffusion-weighted and axial T2-weighted sequences. ASSESSMENT: High-confidence cancer voxels were delineated by expert consensus, using imaging data and biopsy results. The entire prostate was considered benign in patients with no detectable cancer. Diffusion images were used to calculate RSI4 -C1 and conventional ADC. Classifier images were also generated. STATISTICAL TESTS: Voxel-level discrimination of PCa from benign prostate tissue was assessed via receiver operating characteristic (ROC) curves generated by bootstrapping with patient-level case resampling. RSI4 -C1 was compared to conventional ADC for two metrics: area under the ROC curve (AUC) and false-positive rate for a sensitivity of 90% (FPR90 ). Statistical significance was assessed using bootstrap difference with two-sided α = 0.05. RESULTS: RSI4 -C1 outperformed conventional ADC, with greater AUC (mean 0.977 [95% CI: 0.951-0.991] vs. 0.922 [0.878-0.948]) and lower FPR90 (0.032 [0.009-0.082] vs. 0.201 [0.132-0.290]). These improvements were statistically significant (P < 0.05). DATA CONCLUSION: RSI4 -C1 yielded a quantitative, voxel-level classifier of PCa that was superior to conventional ADC. RSI classifier images with a low false-positive rate might improve PCa detection and facilitate clinical applications like targeted biopsy and treatment planning. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Improved Characterization of Diffusion in Normal and Cancerous Prostate Tissue Through Optimization of Multicompartmental Signal Models.

BACKGROUND: Multicompartmental modeling outperforms conventional diffusion-weighted imaging (DWI) in the assessment of prostate cancer. Optimized multicompartmental models could further improve the detection and characterization of prostate cancer. PURPOSE: To optimize multicompartmental signal models and apply them to study diffusion in normal and cancerous prostate tissue in vivo. STUDY TYPE: Retrospective. SUBJECTS: Forty-six patients who underwent MRI examination for suspected prostate cancer; 23 had prostate cancer and 23 had no detectable cancer. FIELD STRENGTH/SEQUENCE: 3T multishell diffusion-weighted sequence. ASSESSMENT: Multicompartmental models with 2-5 tissue compartments were fit to DWI data from the prostate to determine optimal compartmental apparent diffusion coefficients (ADCs). These ADCs were used to compute signal contributions from the different compartments. The Bayesian Information Criterion (BIC) and model-fitting residuals were calculated to quantify model complexity and goodness-of-fit. Tumor contrast-to-noise ratio (CNR) and tumor-to-background signal intensity ratio (SIR) were computed for conventional DWI and multicompartmental signal-contribution maps. STATISTICAL TESTS: Analysis of variance (ANOVA) and two-sample t-tests (α = 0.05) were used to compare fitting residuals between prostate regions and between multicompartmental models. T-tests (α = 0.05) were also used to assess differences in compartmental signal-fraction between tissue types and CNR/SIR between conventional DWI and multicompartmental models. RESULTS: The lowest BIC was observed from the 4-compartment model, with optimal ADCs of 5.2e-4, 1.9e-3, 3.0e-3, and >3.0e-2 mm2 /sec. Fitting residuals from multicompartmental models were significantly lower than from conventional ADC mapping (P < 0.05). Residuals were lowest in the peripheral zone and highest in tumors. Tumor tissue showed the largest reduction in fitting residual by increasing model order. Tumors had a greater proportion of signal from compartment 1 than normal tissue (P < 0.05). Tumor CNR and SIR were greater on compartment-1 signal maps than conventional DWI (P < 0.05) and increased with model order. DATA CONCLUSION: The 4-compartment signal model best described diffusion in the prostate. Compartmental signal contributions revealed by this model may improve assessment of prostate cancer. Level of Evidence 3 Technical Efficacy Stage 3 J. MAGN. RESON. IMAGING 2021;53:628-639.

Exercise-induced calf muscle hyperemia: quantitative mapping with low-dose dynamic contrast enhanced magnetic resonance imaging.

Peripheral artery disease (PAD) in the lower extremities often leads to intermittent claudication. In the present study, we proposed a low-dose DCE MRI protocol for quantifying calf muscle perfusion stimulated with plantar flexion and multiple new metrics for interpreting perfusion maps, including the ratio of gastrocnemius over soleus perfusion (G/S; for assessing the vascular redistribution between the two muscles) and muscle perfusion normalized by whole body perfusion (for quantifying the muscle's active hyperemia). Twenty-eight human subjects participated in this Institutional Review Board-approved study, with 10 healthy subjects ( group A) for assessing interday reproducibility and 8 healthy subjects ( group B) for exploring the relationship between plantar-flexion load and induced muscle perfusion. In a pilot group of five elderly healthy subjects and five patients with PAD ( group C), we proposed a protocol that measured perfusion for a low-intensity exercise and for an exhaustion exercise in a single MRI session. In group A, perfusion estimates for calf muscles were highly reproducible, with correlation coefficients of 0.90-0.93. In group B, gastrocnemius perfusion increased linearly with the exercise workload ( P < 0.05). With the low-intensity exercise, patients with PAD in group C showed substantially lower gastrocnemius perfusion compared with elderly healthy subjects [43.4 (SD 23.5) vs. 106.7 (SD 73.2) ml·min-1·100 g-1]. With exhaustion exercise, G/S [1.0 (SD 0.4)] for patients with PAD was lower than both its low-intensity level [1.9 (SD 1.3)] and the level in elderly healthy subjects [2.7 (SD 2.1)]. In conclusion, the proposed MRI protocol and the new metrics are feasible for quantifying exercise-induced muscle hyperemia, a promising functional test of PAD. NEW & NOTEWORTHY To quantitatively map exercise-induced hyperemia in calf muscles, we proposed a high-resolution MRI method shown to be highly reproducible and sensitive to exercise load. With the use of low contrast, it is feasible to measure calf muscle hyperemia for both low-intensity and exhaustion exercises in a single MRI session. The newly proposed metrics for interpreting perfusion maps are promising for quantifying intermuscle vascular redistribution or a muscle's active hyperemia.

Quantitative characterization of glomerular fibrosis with magnetic resonance imaging: a feasibility study in a rat glomerulonephritis model.

Glomerular fibrosis occurs in the early stages of multiple renal diseases, including hypertensive and diabetic nephropathy. Conventional assessment of glomerular fibrosis relies on kidney biopsy, which is invasive and does not reflect physiological aspects such as blood perfusion. In this study, we sought to assess potential changes of cortical perfusion and microstructure at different degrees of glomerular fibrosis using magnetic resonance imaging (MRI). A rat model of glomerular fibrosis was induced by injecting anti-Thy-1 monoclonal antibody OX-7 to promote mesangial extracellular matrix proliferation. For six rats on day 5 and five rats on day 12 after the induction, we measured renal cortical perfusion and spin-spin relaxation time (T2) in a 3-Tesla MRI scanner. T2 reflects tissue microstructural changes. Glomerular fibrosis severity was evaluated by histological analysis and proteinuria. Four rats without fibrosis were included as controls. In the control rats, the periodic acid-Schiff (PAS)-positive area was 22 ± 1% of total glomerular tuft, which increased significantly to 56 ± 12% and 45 ± 10% in the day 5 and day 12 fibrotic groups, respectively ( P < 0.01). For the three groups (control, day 5, and day 12 after OX-7 injection), cortical perfusion was 7.27 ± 2.54, 3.78 ± 2.17, and 3.32 ± 2.62 ml·min-1·g-1, respectively, decreasing with fibrosis severity ( P < 0.01), and cortical T2 was 75.2 ± 4.6, 84.1 ± 3.0, and 87.9 ± 5.6 ms, respectively ( P < 0.01). In conclusion, extracellular matrix proliferation in glomerular mesangial cells severely diminished blood flow through the glomeruli and also altered cortical microstructure to increase cortical T2. The MRI-measured parameters are proven to be sensitive markers for characterizing glomerular fibrosis.

Performance of an efficient image-registration algorithm in processing MR renography data.

PURPOSE: To evaluate the performance of an edge-based registration technique in correcting for respiratory motion artifacts in magnetic resonance renographic (MRR) data and to examine the efficiency of a semiautomatic software package in processing renographic data from a cohort of clinical patients. MATERIALS AND METHODS: The developed software incorporates an image-registration algorithm based on the generalized Hough transform of edge maps. It was used to estimate glomerular filtration rate (GFR), renal plasma flow (RPF), and mean transit time (MTT) from 36 patients who underwent free-breathing MRR at 3T using saturation-recovery turbo-FLASH. The processing time required for each patient was recorded. Renal parameter estimates and model-fitting residues from the software were compared to those from a previously reported technique. Interreader variability in the software was quantified by the standard deviation of parameter estimates among three readers. GFR estimates from our software were also compared to a reference standard from nuclear medicine. RESULTS: The time taken to process one patient's data with the software averaged 12 ± 4 minutes. The applied image registration effectively reduced motion artifacts in dynamic images by providing renal tracer-retention curves with significantly smaller fitting residues (P < 0.01) than unregistered data or data registered by the previously reported technique. Interreader variability was less than 10% for all parameters. GFR estimates from the proposed method showed greater concordance with reference values (P < 0.05). CONCLUSION: These results suggest that the proposed software can process MRR data efficiently and accurately. Its incorporated registration technique based on the generalized Hough transform effectively reduces respiratory motion artifacts in free-breathing renographic acquisitions.

Exercise-induced calf muscle hyperemia quantified with dynamic blood oxygen level-dependent (BOLD) imaging.

Muscle hyperemia in exercise is usually the combined result of increased cardiac output and local muscle vasodilation, with the latter reflecting muscle's capacity for increased blood perfusion to support exercise. In this study, we aim to quantify muscle's vasodilation capability with dynamic BOLD imaging. A deoxyhemoglobin-kinetics model is proposed to analyze dynamic BOLD signals acquired during exercise recovery, deriving a hyperemia index (HI) for a muscle group of interest. We demonstrated the method's validity with calf muscles of healthy subjects who performed plantar flexion for muscle stimulation. In a test with exercise load incrementally increasing from 0 to 16 lbs., gastrocnemius HI showed considerable variance among the 4 subjects, but with a consistent trend, i.e. low at light load (e.g. 0-6 lbs) and linearly increasing at heavy load. The high variability among different subjects was confirmed with the other 10 subjects who exercised with a same moderate load of 8 lbs., with coefficient of variance among subjects' medial gastrocnemius 87.8%, lateral gastrocnemius 111.8% and soleus 132.3%. These findings align with the fact that intensive exercise induces high muscle hyperemia, but a comparison among different subjects is hard to make, presumably due to the subjects' different rate of oxygen utilization. For the same 10 subjects who exercised with load of 8 lbs., we also performed dynamic contrast enhanced (DCE) MRI to measure muscle perfusion (F). With a moderate correlation of 0.654, HI and F displayed three distinctive responses of calf muscles: soleus of all the subjects were in the cluster of low F and low HI, and gastrocnemius of most subjects had high F and either low or high HI. This finding suggests that parameter F encapsulates blood flow through vessels of all sizes, but BOLD-derived HI focuses on capillary flow and therefore is a more specific indicator of muscle vasodilation. In conclusion, the proposed hyperemia index has the potential of quantitatively assessing muscle vasodilation induced with exercise.

Comparison of synthesized and acquired high b-value diffusion-weighted MRI for detection of prostate cancer.

BACKGROUND: High b-value diffusion-weighted images (DWI) are used for detection of clinically significant prostate cancer (csPCa). This study qualitatively and quantitatively compares synthesized DWI (sDWI) to acquired (aDWI) for detection of csPCa. METHODS: One hundred fifty-one consecutive patients who underwent prostate MRI and biopsy were included in the study. Axial DWI with b = 0, 500, 1000, and 2000 s/mm2 using a 3T clinical scanner using a 32-channel phased-array body coil were acquired. We retrospectively synthesized DWI for b = 2000 s/mm2 via extrapolation based on mono-exponential decay, using b = 0 and b = 500 s/mm2 (sDWI500) and b = 0, b = 500 s/mm2, and b = 1000 s/mm2 (sDWI1000). Differences in signal intensity between sDWI and aDWI were evaluated within different regions of interest (prostate alone, prostate plus 5 mm, 30 mm and 70 mm margin and full field of view). The maximum DWI value within each ROI was evaluated for prediction of csPCa. Classification accuracy was compared to Restriction Spectrum Imaging restriction score (RSIrs), a previously validated biomarker based on multi-exponential DWI. Discrimination of csPCa was evaluated via area under the receiver operating characteristic curve (AUC). RESULTS: Within the prostate, mean ± standard deviation of percent mean differences between sDWI and aDWI signal were -46 ± 35% for sDWI1000 and -67 ± 24% for sDWI500. AUC for aDWI, sDWI500, sDWI1000, and RSIrs within the prostate 0.62[95% confidence interval: 0.53, 0.71], 0.63[0.54, 0.72], 0.65[0.56, 0.73] and 0.78[0.71, 0.86], respectively. CONCLUSION: sDWI is qualitatively comparable to aDWI within the prostate. However, hyperintense artifacts are introduced with sDWI in the surrounding pelvic tissue that interfere with quantitative cancer detection and might mask metastases. In the prostate, RSIrs yields superior quantitative csPCa detection than sDWI or aDWI.

Quantitative MRI biomarker for classification of clinically significant prostate cancer: calibration for reproducibility across echo times.

Background: Restriction Spectrum Imaging restriction score (RSIrs) is a quantitative biomarker for detecting clinically significant prostate cancer (csPCa). However, the quantitative value of the RSIrs is affected by imaging parameters such as echo time (TE). Purpose: The purpose of the present study is to develop a calibration method to account for differences in echo times and facilitate use of RSIrs as a quantitative biomarker for the detection of csPCa. Methods: This study included 197 consecutive patients who underwent MRI and biopsy examination; 97 were diagnosed with csPCa (grade group ≥ 2). RSI data were acquired three times during the same session: twice at minimum TE∼75ms and once at TE=90ms (TEmin 1 , TEmin 2 , and TE90, respectively). A proposed calibration method, trained on patients without csPCa, estimated a linear scaling factor (f) for each of the four diffusion compartments (C) of the RSI signal model. A linear regression model was determined to match C-maps of TE90 to the reference C-maps of TEmin 1 within the interval ranging from 95 th to 99 th percentile of signal intensity within the prostate. RSIrs comparisons were made at 98 th percentile within each patient's prostate. We compared RSIrs from calibrated TE90 (RSIrs TE90corr ) and uncorrected TE90 (RSIrs TE90 ) to RSIrs from reference TEmin 1 (RSIrs TEmin1 ) and repeated TEmin 2 (RSIrs TEmin2 ). Calibration performance was evaluated with sensitivity, specificity, area under the ROC curve, positive predicted value, negative predicted value, and F1-score. Results: Scaling factors for C 1 , C 2 , C 3 , and C 4 were estimated as 1.70, 1.38, 1.03, and 1.19, respectively. In non-csPCa cases, the 98 th percentile of RSIrs TEmin2 and RSIrs TEmin1 differed by 0.27±0.86SI (mean±standard deviation), whereas RSIrs TE90 differed from RSIrs TEmin1 by 1.81±1.20SI. After calibration, this bias was reduced to -0.41±1.20SI, representing a 78% reduction in absolute error. For patients with csPCa, the difference was 0.54±1.98SI between RSIrs TEmin2 and RSIrs TEmin1 and 2.28±2.06SI between RSIrs TE90 and RSIrs TEmin1 . After calibration, the mean difference decreased to -0.86SI, a 38% reduction in absolute error. At the Youden index for patient-level classification of csPCa (8.94SI), RSIrs TEmin1 has a sensitivity of 66% and a specificity of 72%. Prior to calibration, RSIrs TE90 at the same threshold tended to over-diagnose benign cases (sensitivity 44%, specificity 88%). Post-calibration, RSIrs TE90corr performs more similarly to the reference (sensitivity 71%, specificity 62%). Conclusion: The proposed linear calibration method produces similar quantitative biomarker values for acquisitions with different TE, reducing TE-induced error by 78% and 38% for non-csPCa and csPCa, respectively.

Clinical Impact of Contouring Variability for Prostate Cancer Tumor Boost.

PURPOSE: The focal radiation therapy (RT) boost technique was shown in a phase III randomized controlled trial (RCT) to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. A recent prospective study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists' contour inaccuracies would yield meaningfully worse clinical outcomes. METHODS AND MATERIALS: Forty-five radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the RCT protocol. The probability of biochemical failure (BF) was determined using a model from the RCT. The primary metric evaluated was delta BF (DBF = Participant BF - Expert BF). An absolute increase in BF ≥5% was considered clinically meaningful. RESULTS: Eight patient cases and 394 target volumes for focal RT boost planning were included in this analysis. In general, participant plans were associated with worse predicted clinical outcomes compared to the expert plan, with an average absolute increase in BF of 4.3%. Of participant plans, 37% were noted to have an absolute increase in BF of 5% or more. CONCLUSIONS: Radiation oncologists' attempts to contour tumor targets for focal RT boost are frequently inaccurate enough to yield meaningfully inferior clinical outcomes for patients.

Deep Learning Segmentation of Infiltrative and Enhancing Cellular Tumor at Pre- and Posttreatment Multishell Diffusion MRI of Glioblastoma.

Purpose To develop and validate a deep learning (DL) method to detect and segment enhancing and nonenhancing cellular tumor on pre- and posttreatment MRI scans in patients with glioblastoma and to predict overall survival (OS) and progression-free survival (PFS). Materials and Methods This retrospective study included 1397 MRI scans in 1297 patients with glioblastoma, including an internal set of 243 MRI scans (January 2010 to June 2022) for model training and cross-validation and four external test cohorts. Cellular tumor maps were segmented by two radiologists on the basis of imaging, clinical history, and pathologic findings. Multimodal MRI data with perfusion and multishell diffusion imaging were inputted into a nnU-Net DL model to segment cellular tumor. Segmentation performance (Dice score) and performance in distinguishing recurrent tumor from posttreatment changes (area under the receiver operating characteristic curve [AUC]) were quantified. Model performance in predicting OS and PFS was assessed using Cox multivariable analysis. Results A cohort of 178 patients (mean age, 56 years ± 13 [SD]; 116 male, 62 female) with 243 MRI timepoints, as well as four external datasets with 55, 70, 610, and 419 MRI timepoints, respectively, were evaluated. The median Dice score was 0.79 (IQR, 0.53-0.89), and the AUC for detecting residual or recurrent tumor was 0.84 (95% CI: 0.79, 0.89). In the internal test set, estimated cellular tumor volume was significantly associated with OS (hazard ratio [HR] = 1.04 per milliliter; P < .001) and PFS (HR = 1.04 per milliliter; P < .001) after adjustment for age, sex, and gross total resection (GTR) status. In the external test sets, estimated cellular tumor volume was significantly associated with OS (HR = 1.01 per milliliter; P < .001) after adjustment for age, sex, and GTR status. Conclusion A DL model incorporating advanced imaging could accurately segment enhancing and nonenhancing cellular tumor, distinguish recurrent or residual tumor from posttreatment changes, and predict OS and PFS in patients with glioblastoma. Keywords: Segmentation, Glioblastoma, Multishell Diffusion MRI Supplemental material is available for this article. © RSNA, 2024.

Comparison of synthesized and acquired high b -value diffusion-weighted MRI for detection of prostate cancer.

Background: High b -value diffusion-weighted images (DWI) are used for detection of clinically significant prostate cancer (csPCa). To decrease scan time and improve signal-to-noise ratio, high b -value (>1000 s/mm 2 ) images are often synthesized instead of acquired. Purpose: Qualitatively and quantitatively compare synthesized DWI (sDWI) to acquired (aDWI) for detection of csPCa. Study Type: Retrospective. Subjects: 151 consecutive patients who underwent prostate MRI and biopsy. Sequence: Axial DWI with b =0, 500, 1000, and 2000 s/mm 2 using a 3T clinical scanner using a 32-channel phased-array body coil. Assessment: We synthesized DWI for b =2000 s/mm 2 via extrapolation based on monoexponential decay, using b =0 and b =500 s/mm 2 (sDWI 500 ) and b =0, b =500, and b =1000 s/mm 2 (sDWI 1000 ). Differences between sDWI and aDWI were evaluated within regions of interest (ROIs). The maximum DWI value within each ROI was evaluated for prediction of csPCa. Classification accuracy was also compared to Restriction Spectrum Imaging restriction score (RSIrs), a previously validated biomarker based on multi-exponential DWI. Statistical Tests: Discrimination of csPCa was evaluated via area under the receiver operating characteristic curve (AUC). Statistical significance was assessed using bootstrap difference (two-sided α=0.05). Results: Within the prostate, mean ± standard deviation of percent mean differences between sDWI and aDWI signal were -46±35% for sDWI 1000 and -67±24% for sDWI 500 . AUC for aDWI, sDWI 500, sDWI 1000 , and RSIrs within the prostate 0.62[95% confidence interval: 0.53, 0.71], 0.63[0.54, 0.72], 0.65[0.56, 0.73] and 0.78[0.71, 0.86], respectively. When considering the whole field of view, classification accuracy and qualitative image quality decreased notably for sDWI compared to aDWI and RSIrs. Data Conclusion: sDWI is qualitatively comparable to aDWI within the prostate. However, hyperintense artifacts are introduced with sDWI in the surrounding pelvic tissue that interfere with quantitative cancer detection and might mask metastases. In the prostate, RSIrs yields superior quantitative csPCa detection than sDWI or aDWI.

A Multicompartmental Diffusion Model for Improved Assessment of Whole-Body Diffusion-weighted Imaging Data and Evaluation of Prostate Cancer Bone Metastases.

Purpose To develop a multicompartmental signal model for whole-body diffusion-weighted imaging (DWI) and apply it to study the diffusion properties of normal tissue and metastatic prostate cancer bone lesions in vivo. Materials and Methods This prospective study (ClinicalTrials.gov: NCT03440554) included 139 men with prostate cancer (mean age, 70 years ± 9 [SD]). Multicompartmental models with two to four tissue compartments were fit to DWI data from whole-body scans to determine optimal compartmental diffusion coefficients. Bayesian information criterion (BIC) and model-fitting residuals were calculated to quantify model complexity and goodness of fit. Diffusion coefficients for the optimal model (having lowest BIC) were used to compute compartmental signal-contribution maps. The signal intensity ratio (SIR) of bone lesions to normal-appearing bone was measured on these signal-contribution maps and on conventional DWI scans and compared using paired t tests (α = .05). Two-sample t tests (α = .05) were used to compare compartmental signal fractions between lesions and normal-appearing bone. Results Lowest BIC was observed from the four-compartment model, with optimal compartmental diffusion coefficients of 0, 1.1 × 10-3, 2.8 × 10-3, and >3.0 ×10-2 mm2/sec. Fitting residuals from this model were significantly lower than from conventional apparent diffusion coefficient mapping (P < .001). Bone lesion SIR was significantly higher on signal-contribution maps of model compartments 1 and 2 than on conventional DWI scans (P < .008). The fraction of signal from compartments 2, 3, and 4 was also significantly different between metastatic bone lesions and normal-appearing bone tissue (P ≤ .02). Conclusion The four-compartment model best described whole-body diffusion properties. Compartmental signal contributions from this model can be used to examine prostate cancer bone involvement. Keywords: Whole-Body MRI, Diffusion-weighted Imaging, Restriction Spectrum Imaging, Diffusion Signal Model, Bone Metastases, Prostate Cancer Clinical trial registration no. NCT03440554 Supplemental material is available for this article. © RSNA, 2023 See also commentary by Margolis in this issue.

ReIGNITE Radiation Therapy Boost: A Prospective, International Study of Radiation Oncologists' Accuracy in Contouring Prostate Tumors for Focal Radiation Therapy Boost on Conventional Magnetic Resonance Imaging Alone or With Assistance of Restriction Spectrum Imaging.

PURPOSE: In a phase III randomized trial, adding a radiation boost to tumor(s) visible on MRI improved prostate cancer (PCa) disease-free and metastasis-free survival without additional toxicity. Radiation oncologists' ability to identify prostate tumors is critical to widely adopting intraprostatic tumor radiotherapy boost for patients. A diffusion MRI biomarker, called the Restriction Spectrum Imaging restriction score (RSIrs), has been shown to improve radiologists' identification of clinically significant PCa. We hypothesized that (1) radiation oncologists would find accurately delineating PCa tumors on conventional MRI challenging and (2) using RSIrs maps would improve radiation oncologists' accuracy for PCa tumor delineation. METHODS AND MATERIALS: In this multi-institutional, international, prospective study, 44 radiation oncologists (participants) and 2 expert radiologists (experts) contoured prostate tumors on 39 total patient cases using conventional MRI with or without RSIrs maps. Participant volumes were compared to the consensus expert volumes. Contouring accuracy metrics included percent overlap with expert volume, Dice coefficient, conformal number, and maximum distance beyond expert volume. RESULTS: 1604 participant volumes were produced. 40 of 44 participants (91%) completely missed ≥1 expert-defined target lesion without RSIrs, compared to 13 of 44 (30%) with RSIrs maps. On conventional MRI alone, 134 of 762 contour attempts (18%) completely missed the target, compared to 18 of 842 (2%) with RSIrs maps. Use of RSIrs maps improved all contour accuracy metrics by approximately 50% or more. Mixed effects modeling confirmed that RSIrs maps were the main variable driving improvement in all metrics. System Usability Scores indicated RSIrs maps significantly improved the contouring experience (72 vs. 58, p < 0.001). CONCLUSIONS: Radiation oncologists struggle with accurately delineating visible PCa tumors on conventional MRI. RSIrs maps improve radiation oncologists' ability to target MRI-visible tumors for prostate tumor boost.

Automated Patient-level Prostate Cancer Detection with Quantitative Diffusion Magnetic Resonance Imaging.

Background: Multiparametric magnetic resonance imaging (mpMRI) improves detection of clinically significant prostate cancer (csPCa), but the subjective Prostate Imaging Reporting and Data System (PI-RADS) system and quantitative apparent diffusion coefficient (ADC) are inconsistent. Restriction spectrum imaging (RSI) is an advanced diffusion-weighted MRI technique that yields a quantitative imaging biomarker for csPCa called the RSI restriction score (RSIrs). Objective: To evaluate RSIrs for automated patient-level detection of csPCa. Design setting and participants: We retrospectively studied all patients (n = 151) who underwent 3 T mpMRI and RSI (a 2-min sequence on a clinical scanner) for suspected prostate cancer at University of California San Diego during 2017-2019 and had prostate biopsy within 180 d of MRI. Intervention: We calculated the maximum RSIrs and minimum ADC within the prostate, and obtained PI-RADS v2.1 from medical records. Outcome measurements and statistical analysis: We compared the performance of RSIrs, ADC, and PI-RADS for the detection of csPCa (grade group ≥2) on the best available histopathology (biopsy or prostatectomy) using the area under the curve (AUC) with two-tailed α = 0.05. We also explored whether the combination of PI-RADS and RSIrs might be superior to PI-RADS alone and performed subset analyses within the peripheral and transition zones. Results and limitations: AUC values for ADC, RSIrs, and PI-RADS were 0.48 (95% confidence interval: 0.39, 0.58), 0.78 (0.70, 0.85), and 0.77 (0.70, 0.84), respectively. RSIrs and PI-RADS were each superior to ADC for patient-level detection of csPCa (p < 0.0001). RSIrs alone was comparable with PI-RADS (p = 0.8). The combination of PI-RADS and RSIrs had an AUC of 0.85 (0.78, 0.91) and was superior to either PI-RADS or RSIrs alone (p < 0.05). Similar patterns were seen in the peripheral and transition zones. Conclusions: RSIrs is a promising quantitative marker for patient-level csPCa detection, warranting a prospective study. Patient summary: We evaluated a rapid, advanced prostate magnetic resonance imaging technique called restriction spectrum imaging to see whether it could give an automated score that predicted the presence of clinically significant prostate cancer. The automated score worked about as well as expert radiologists' interpretation. The combination of the radiologists' scores and automated score might be better than either alone.

Correcting B0 inhomogeneity-induced distortions in whole-body diffusion MRI of bone.

Diffusion-weighted magnetic resonance imaging (DWI) of the musculoskeletal system has various applications, including visualization of bone tumors. However, DWI acquired with echo-planar imaging is susceptible to distortions due to static magnetic field inhomogeneities. This study aimed to estimate spatial displacements of bone and to examine whether distortion corrected DWI images more accurately reflect underlying anatomy. Whole-body MRI data from 127 prostate cancer patients were analyzed. The reverse polarity gradient (RPG) technique was applied to DWI data to estimate voxel-level distortions and to produce a distortion corrected DWI dataset. First, an anatomic landmark analysis was conducted, in which corresponding vertebral landmarks on DWI and anatomic T2-weighted images were annotated. Changes in distance between DWI- and T2-defined landmarks (i.e., changes in error) after distortion correction were calculated. In secondary analyses, distortion estimates from RPG were used to assess spatial displacements of bone metastases. Lastly, changes in mutual information between DWI and T2-weighted images of bone metastases after distortion correction were calculated. Distortion correction reduced anatomic error of vertebral DWI up to 29 mm. Error reductions were consistent across subjects (Wilcoxon signed-rank p < 10-20). On average (± SD), participants' largest error reduction was 11.8 mm (± 3.6). Mean (95% CI) displacement of bone lesions was 6.0 mm (95% CI 5.0-7.2); maximum displacement was 17.1 mm. Corrected diffusion images were more similar to structural MRI, as evidenced by consistent increases in mutual information (Wilcoxon signed-rank p < 10-12). These findings support the use of distortion correction techniques to improve localization of bone on DWI.

Tri-Compartmental Restriction Spectrum Imaging Breast Model Distinguishes Malignant Lesions from Benign Lesions and Healthy Tissue on Diffusion-Weighted Imaging.

Diffusion-weighted MRI (DW-MRI) offers a potential adjunct to dynamic contrast-enhanced MRI to discriminate benign from malignant breast lesions by yielding quantitative information about tissue microstructure. Multi-component modeling of the DW-MRI signal over an extended b-value range (up to 3000 s/mm2) theoretically isolates the slowly diffusing (restricted) water component in tissues. Previously, a three-component restriction spectrum imaging (RSI) model demonstrated the ability to distinguish malignant lesions from healthy breast tissue. We further evaluated the utility of this three-component model to differentiate malignant from benign lesions and healthy tissue in 12 patients with known malignancy and synchronous pathology-proven benign lesions. The signal contributions from three distinct diffusion compartments were measured to generate parametric maps corresponding to diffusivity on a voxel-wise basis. The three-component model discriminated malignant from benign and healthy tissue, particularly using the restricted diffusion C1 compartment and product of the restricted and intermediate diffusion compartments (C1 and C2). However, benign lesions and healthy tissue did not significantly differ in diffusion characteristics. Quantitative discrimination of these three tissue types (malignant, benign, and healthy) in non-pre-defined lesions may enhance the clinical utility of DW-MRI in reducing excessive biopsies and aiding in surveillance and surgical evaluation without repeated exposure to gadolinium contrast.

Discrimination of Breast Cancer from Healthy Breast Tissue Using a Three-component Diffusion-weighted MRI Model.

PURPOSE: Diffusion-weighted MRI (DW-MRI) is a contrast-free modality that has demonstrated ability to discriminate between predefined benign and malignant breast lesions. However, how well DW-MRI discriminates cancer from all other breast tissue voxels in a clinical setting is unknown. Here we explore the voxelwise ability to distinguish cancer from healthy breast tissue using signal contributions from the newly developed three-component multi-b-value DW-MRI model. EXPERIMENTAL DESIGN: Patients with pathology-proven breast cancer from two datasets (n = 81 and n = 25) underwent multi-b-value DW-MRI. The three-component signal contributions C 1 and C 2 and their product, C 1 C 2, and signal fractions F 1, F 2, and F 1 F 2 were compared with the image defined on maximum b-value (DWI max), conventional apparent diffusion coefficient (ADC), and apparent diffusion kurtosis (K app). The ability to discriminate between cancer and healthy breast tissue was assessed by the false-positive rate given a sensitivity of 80% (FPR80) and ROC AUC. RESULTS: Mean FPR80 for both datasets was 0.016 [95% confidence interval (CI), 0.008-0.024] for C 1 C 2, 0.136 (95% CI, 0.092-0.180) for C 1, 0.068 (95% CI, 0.049-0.087) for C 2, 0.462 (95% CI, 0.425-0.499) for F 1 F 2, 0.832 (95% CI, 0.797-0.868) for F 1, 0.176 (95% CI, 0.150-0.203) for F 2, 0.159 (95% CI, 0.114-0.204) for DWI max, 0.731 (95% CI, 0.692-0.770) for ADC, and 0.684 (95% CI, 0.660-0.709) for K app. Mean ROC AUC for C 1 C 2 was 0.984 (95% CI, 0.977-0.991). CONCLUSIONS: The C 1 C 2 parameter of the three-component model yields a clinically useful discrimination between cancer and healthy breast tissue, superior to other DW-MRI methods and obliviating predefining lesions. This novel DW-MRI method may serve as noncontrast alternative to standard-of-care dynamic contrast-enhanced MRI.