Diffusion-weighted imaging (DWI) is routinely used to aid in the detection and characterization of prostate cancer. Given imaging time constraints in a clinical setting, it is important to maximize the statistical efficiency of a DWI examination of the prostate. The objective is to maximize the accuracy with which microstructural information about the prostate can be obtained while minimizing diffusion scan time. In this study, we apply estimation theory to evaluate the statistical efficiency of different DWI acquisitions and methods. Specifically, we show that the variance of DWI parameters estimated using nonlinear multiexponential signal models is considerably higher than the variance observed using linear signal models. We then derive a simple analytical expression for the efficiency of a linear estimator and use it to optimize b -value sampling for DWI of the prostate.

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, sDWI_500, 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.

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.

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.

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.

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.

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.

Abstract: Purpose: Multiparametric MRI (mpMRI) improves detection of clinically significant prostate cancer (csPCa), but the qualitative PI-RADS system and quantitative apparent diffusion coefficient (ADC) yield inconsistent results. An advanced Restrictrion Spectrum Imaging (RSI) model may yield a better quantitative marker for csPCa, the RSI restriction score (RSIrs). We evaluated RSIrs for patient-level detection of csPCa. Materials and Methods: Retrospective analysis of men who underwent mpMRI with RSI and prostate biopsy for suspected prostate cancer from 2017-2019. Maximum RSIrs within the prostate was assessed by area under the receiver operating characteristic curve (AUC) for discriminating csPCa (grade group ≥2) from benign or grade group 1 biopsies. Performance of RSIrs was compared to minimum ADC and PI-RADS v2-2.1via bootstrap confidence intervals and bootstrap difference (two-tailed α=0.05). We also tested whether the combination of PI-RADS and RSIrs (PI-RADS+RSIrs) was superior to PI-RADS, alone. Results: 151 patients met criteria for inclusion. AUC values for ADC, RSIrs, and PI-RADS were 0.50 [95% confidence interval: 0.41, 0.60], 0.76 [0.68, 0.84], and 0.78 [0.71, 0.85], respectively. RSIrs (p=0.0002) and PI-RADS (p<0.0001) were superior to ADC for patient-level detection of csPCa. The performance of RSIrs was comparable to that of PI-RADS (p=0.6). AUC for PI-RADS+RSIrs was 0.84 [0.77, 0.90], superior to PI-RADS or RSIrs, alone (p=0.008, p=0.009). Conclusions: RSIrs was superior to conventional ADC and comparable to (routine, clinical) PI-RADS for patient-level detection of csPCa. The combination of PI-RADS and RSIrs was superior to either alone. RSIrs is a promising quantitative marker worthy of prospective study in the setting of csPCa detection. Disclosures: MEH reports honoraria from Multimodal Imaging Services Corporation and research funding from General Electric Healthcare. AMD is a Founder of and holds equity in CorTechs Labs, Inc, and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. and receives funding through research agreements with General Electric Healthcare. The terms of these arrangements have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies. TMS reports honoraria from Multimodal Imaging Services Corporation, Varian Medical Systems, and WebMD; he has an equity interest in CorTechs Labs, Inc. and also serves on its Scientific Advisory Board. These companies might potentially benefit from the research results. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies.

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 D_1,3 = 0, D_2,3 = 1.5 × 10^-3 , and D_3,3 = 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.

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.