The ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): Results from the OSIPI-Dynamic Contrast-Enhanced challenge.

PURPOSE: K trans $$ {K}^{\mathrm{trans}} $$ has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for K trans $$ {K}^{\mathrm{trans}} $$ quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging-Dynamic Contrast-Enhanced (OSIPI-DCE) challenge was designed to benchmark methods to better help the efforts to standardize K trans $$ {K}^{\mathrm{trans}} $$ measurement. METHODS: A framework was created to evaluate K trans $$ {K}^{\mathrm{trans}} $$ values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for K trans $$ {K}^{\mathrm{trans}} $$ quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' K trans $$ {K}^{\mathrm{trans}} $$ values, the applied software, and a standard operating procedure. These were evaluated using the proposed OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score defined with accuracy, repeatability, and reproducibility components. RESULTS: Across the 10 received submissions, the OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0-1 = lowest-highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in K trans $$ {K}^{\mathrm{trans}} $$ analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. CONCLUSIONS: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within K trans $$ {K}^{\mathrm{trans}} $$ estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology.

Quantitative Characterization of Respiratory Patterns on Dynamic Higher Temporal Resolution MRI to Stratify Postacute Covid-19 Patients by Cardiopulmonary Symptom Burden.

BACKGROUND: Postacute Covid-19 patients commonly present with respiratory symptoms; however, a noninvasive imaging method for quantitative characterization of respiratory patterns is lacking. PURPOSE: To evaluate if quantitative characterization of respiratory pattern on free-breathing higher temporal resolution MRI stratifies patients by cardiopulmonary symptom burden. STUDY TYPE: Prospective analysis of retrospectively acquired data. SUBJECTS: A total of 37 postacute Covid-19 patients (25 male; median [interquartile range (IQR)] age: 58 [42-64] years; median [IQR] days from acute infection: 335 [186-449]). FIELD STRENGTH/SEQUENCE: 0.55 T/two-dimensional coronal true fast imaging with steady-state free precession (trueFISP) at higher temporal resolution. ASSESSMENT: Patients were stratified into three groups based on presence of no (N = 11), 1 (N = 14), or ≥2 (N = 14) cardiopulmonary symptoms, assessed using a standardized symptom inventory within 1 month of MRI. An automated lung postprocessing workflow segmented each lung in each trueFISP image (temporal resolution 0.2 seconds) and respiratory curves were generated. Quantitative parameters were derived including tidal lung area, rates of inspiration and expiration, lung area coefficient of variability (CV), and respiratory incoherence (departure from sinusoidal pattern) were. Pulmonary function tests were recorded if within 1 month of MRI. Qualitative assessment of respiratory pattern and lung opacity was performed by three independent readers with 6, 9, and 23 years of experience. STATISTICAL TESTS: Analysis of variance to assess differences in demographic, clinical, and quantitative MRI parameters among groups; univariable analysis and multinomial logistic regression modeling to determine features predictive of patient symptom status; Akaike information criterion to compare the quality of regression models; Cohen and Fleiss kappa (κ) to quantify inter-reader reliability. Two-sided 5% significance level was used. RESULTS: Tidal area and lung area CV were significantly higher in patients with two or more symptoms than in those with one or no symptoms (area: 15.4 cm2 vs. 12.9 cm2 vs. 12.8 cm2 ; CV: 0.072, 0.067, and 0.058). Respiratory incoherence was significantly higher in patients with two or more symptoms than in those with one or no symptoms (0.05 vs. 0.043 vs. 0.033). There were no significant differences in patient age (P = 0.19), sex (P = 0.88), lung opacity severity (P = 0.48), or pulmonary function tests (P = 0.35-0.97) among groups. Qualitative reader assessment did not distinguish between groups and showed slight inter-reader agreement (κ = 0.05-0.11). DATA CONCLUSION: Quantitative respiratory pattern measures derived from dynamic higher-temporal resolution MRI have potential to stratify patients by symptom burden in a postacute Covid-19 cohort. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Spatial profiling of in vivo diffusion-weighted MRI parameters in the healthy human kidney.

OBJECTIVE: Diffusion-weighted MRI is a technique that can infer microstructural and microcirculatory features from biological tissue, with particular application to renal tissue. There is extensive literature on diffusion tensor imaging (DTI) of anisotropy in the renal medulla, intravoxel incoherent motion (IVIM) measurements separating microstructural from microcirculation effects, and combinations of the two. However, interpretation of these features and adaptation of more specific models remains an ongoing challenge. One input to this process is a whole organ distillation of corticomedullary contrast of diffusion metrics, as has been explored for other renal biomarkers. MATERIALS AND METHODS: In this work, we probe the spatial dependence of diffusion MRI metrics with concentrically layered segmentation in 11 healthy kidneys at 3 T. The metrics include those from DTI, IVIM, a combined approach titled "REnal Flow and Microstructure AnisotroPy (REFMAP)", and a multiply encoded model titled "FC-IVIM" providing estimates of fluid velocity and branching length. RESULTS: Fractional anisotropy decreased from the inner kidney to the outer kidney with the strongest layer correlation in both parenchyma (including cortex and medulla) and medulla with Spearman correlation coefficients and p-values (r, p) of (0.42, <0.001) and (0.37, <0.001), respectively. Also, dynamic parameters derived from the three models significantly decreased with a high correlation from the inner to the outer parenchyma or medulla with (r, p) ranges of (0.46-0.55, <0.001). CONCLUSIONS: These spatial trends might find implications for indirect assessments of kidney physiology and microstructure using diffusion MRI.

Multisite MRI Intravoxel Incoherent Motion Repeatability and Reproducibility across 3 T Scanners in a Breast Diffusion Phantom: A BReast Intravoxel Incoherent Motion Multisite (BRIMM) Study.

BACKGROUND: Monoexponential apparent diffusion coefficient (ADC) and biexponential intravoxel incoherent motion (IVIM) analysis of diffusion-weighted imaging is helpful in the characterization of breast tumors. However, repeatability/reproducibility studies across scanners and across sites are scarce. PURPOSE: To evaluate the repeatability and reproducibility of ADC and IVIM parameters (tissue diffusivity (Dt ), perfusion fraction (Fp ) and pseudo-diffusion (Dp )) within and across sites employing MRI scanners from different vendors utilizing 16-channel breast array coils in a breast diffusion phantom. STUDY TYPE: Phantom repeatability. PHANTOM: A breast phantom containing tubes of different polyvinylpyrrolidone (PVP) concentrations, water, fat, and sponge flow chambers, together with an MR-compatible liquid crystal (LC) thermometer. FIELD STRENGTH/SEQUENCE: Bipolar gradient twice-refocused spin echo sequence and monopolar gradient single spin echo sequence at 3 T. ASSESSMENT: Studies were performed twice in each of two scanners, located at different sites, on each of 2 days, resulting in four studies per scanner. ADCs of the PVP and water were normalized to the vendor-provided calibrated values at the temperature indicated by the LC thermometer for repeatability/reproducibility comparisons. STATISTICAL TESTS: ADC and IVIM repeatability and reproducibility within and across sites were estimated via the within-system coefficient of variation (wCV). Pearson correlation coefficient (r) was also computed between IVIM metrics and flow speed. A P value <0.05 was considered statistically significant. RESULTS: ADC and Dt demonstrated excellent repeatability (<2%; <3%, respectively) and reproducibility (both <5%) at the two sites. Fp and Dp exhibited good repeatability (mean of two sites 3.67% and 5.59%, respectively) and moderate reproducibility (mean of two sites 15.96% and 13.3%, respectively). The mean intersite reproducibility (%) of Fp /Dp /Dt was 50.96/13.68/5.59, respectively. Fp and Dt demonstrated high correlations with flow speed while Dp showed lower correlations. Fp correlations with flow speed were significant at both sites. DATA CONCLUSION: IVIM reproducibility results were promising and similar to ADC, particularly for Dt . The results were reproducible within both sites, and a progressive trend toward reproducibility across sites except for Fp . LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Cardiac Phase and Flow Compensation Effects on REnal Flow and Microstructure AnisotroPy MRI in Healthy Human Kidney.

BACKGROUND: Renal diffusion-weighted imaging (DWI) involves microstructure and microcirculation, quantified with diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM), and hybrid models. A better understanding of their contrast may increase specificity. PURPOSE: To measure modulation of DWI with cardiac phase and flow-compensated (FC) diffusion gradient waveforms. STUDY TYPE: Prospective. POPULATION: Six healthy volunteers (ages: 22-48 years, five females), water phantom. FIELD STRENGTH/SEQUENCE: 3-T, prototype DWI sequence with 2D echo-planar imaging, and bipolar (BP) or FC gradients. 2D Half-Fourier Single-shot Turbo-spin-Echo (HASTE). Multiple-phase 2D spoiled gradient-echo phase contrast (PC) MRI. ASSESSMENT: BP and FC water signal decays were qualitatively compared. Renal arteries and velocities were visualized on PC-MRI. Systolic (peak velocity), diastolic (end stable velocity), and pre-systolic (before peak velocity) phases were identified. Following mutual information-based retrospective self-registration of DWI within each kidney, and Marchenko-Pastur Principal Component Analysis (MPPCA) denoising, combined IVIM-DTI analysis estimated mean diffusivity (MD), fractional anisotropy (FA), and eigenvalues (λi) from tissue diffusivity (Dt ), perfusion fraction (fp ), and pseudodiffusivity (Dp , Dp,axial , Dp,radial ), for each tissue (cortex/medulla, segmented on b0/FA respectively), phase, and waveform (BP, FC). Monte Carlo water diffusion simulations aided data interpretation. STATISTICAL TESTS: Mixed model regression probed differences between tissue types and pulse sequences. Univariate general linear model analysis probed variations among cardiac phases. Spearman correlations were measured between diffusion metrics and renal artery velocities. Statistical significance level was set at P < 0.05. RESULTS: Water BP and FC signal decays showed no differences. Significant pulse sequence dependence occurred for λ1 , λ3 , FA, Dp , fp , Dp,axial , Dp,radial in cortex and medulla, and medullary λ2 . Significant cortex/medulla differences occurred with BP for all metrics except MD (systole [P = 0.224]; diastole [P = 0.556]). Significant phase dependence occurred for Dp , Dp,axial , Dp,radial for BP and medullary λ1 , λ2 , λ3 , MD for FC. FA correlated significantly with velocity. Monte Carlo simulations indicated medullary measurements were consistent with a 34 µm tubule diameter. DATA CONCLUSION: Cardiac gating and flow compensation modulate of measurements of renal diffusion. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 2.

Prostate cancer heterogeneity: texture analysis score based on multiple magnetic resonance imaging sequences for detection, stratification and selection of lesions at time of biopsy.

OBJECTIVE: To undertake an early proof-of-concept study on a novel, semi-automated texture-based scoring system in order to enhance the association between magnetic resonance imaging (MRI) lesions and clinically significant prostate cancer (SPCa). PATIENTS AND METHODS: With ethics approval, 536 imaging volumes were generated from 20 consecutive patients who underwent multiparametric MRI (mpMRI) at time of biopsy. Volumes of interest (VOIs) included zonal anatomy segmentation and suspicious MRI lesions for cancer (Likert Scale score >2). Entropy (E), measuring heterogeneity, was computed from VOIs and plotted as a multiparametric score defined as the entropy score (ES) = E ADC + E Ktrans + E Ve + E T2WI. The reference test that was used to define the ground truth comprised systematic saturation biopsies coupled with MRI-targeted sampling. This generated 422 cores in all that were individually labelled and oriented in three-dimensions. Diagnostic accuracy for detection of SPCa, defined as Gleason score ≥3 + 4 or >3 mm of any grade of cancer on a single core, was assessed using receiver operating characteristics, correlation, and descriptive statistics. The proportion of cancerous lesions detected by ES and visual scoring (VS) were statistically compared using the paired McNemar test. RESULTS: Any cancer (Gleason score 6-8) was found in 12 of the 20 (60%) patients, with a median PSA level of 8.22 ng/mL. SPCa (mean [95% confidence interval, CI] ES = 17.96 [0.72] NATural information unit [NAT]) had a significantly higher ES than non-SPCa (mean [95% CI] ES = 15.33 [0.76] NAT). The ES correlated with Gleason score (rs = 0.568, P = 0.033) and maximum cancer core length (ρ = 0.781; P < 0.001). The area under the curve for the ES (0.89) and VS (0.91) were not significantly different (P = 0.75) for the detection of SPCa amongst MRI lesions. Best ES estimated numerical threshold of 16.61 NAT led to a sensitivity of 100% and negative predictive value of 100%. The proportion of MRI lesions that were found to be positive for SPCa using this ES threshold (54%) was significantly higher (P < 0.001) than using the VS (24% of score 3, 4, 5) in a paired analysis using the McNemar test. In all, 53% of MRI lesions would have avoided biopsy sampling without missing significant disease. CONCLUSION: Capturing heterogeneity of prostate cancer across multiple MRI sequences with the ES yielded high performances for the detection and stratification of SPCa. The ES outperformed the VS in predicting positivity of lesions, holding promise in the selection of targets for biopsy and calling for further understanding of this association.

REnal Flow and Microstructure AnisotroPy (REFMAP) MRI in Normal and Peritumoral Renal Tissue.

BACKGROUND: Diffusion-weighted imaging (DWI) provides insight into the pathophysiology underlying renal dysfunction. Variants of DWI include intravoxel incoherent motion (IVIM), which differentiates between microstructural diffusion and vascular or tubular flow, and diffusion tensor imaging (DTI), which quantifies diffusion directionality. PURPOSE: To investigate the reproducibility of joint IVIM-DTI and compare controls to presurgical renal mass patients. STUDY TYPE: Prospective cross-sectional. SUBJECTS: Thirteen healthy controls and ten presurgical renal mass patients were scanned. Ten controls were scanned twice to investigate reproducibility. FIELD STRENGTH/SEQUENCE: Subjects were scanned on a 3T system using 10 b-values and 20 diffusion directions for IVIM-DTI in a study approved by the local Institutional Review Board. ASSESSMENT: Retrospective coregistration and measurement of joint IVIM-DTI parameters were performed. STATISTICAL ANALYSIS: Parameter reproducibility was defined as intraclass correlation coefficient (ICC) >0.7 and coefficient of variation (CV) <30%. Patient data were stratified by lesion side (contralateral/ipsilateral) for comparison with controls. Corticomedullary differentiation was evaluated. RESULTS: In controls, the reproducible subset of REnal Flow and Microstructure AnisotroPy (REFMAP) parameters had average ICC = 0.82 and CV = 7.5%. In renal mass patients, medullary fractional anisotropy (FA) was significantly lower than in controls (0.227 ± 0.072 vs. 0.291 ± 0.044, P = 0.016 for the kidney contralateral to the mass and 0.228 ± 0.070 vs. 0.291 ± 0.044, P = 0.018 for the kidney ipsilateral). In the kidney ipsilateral to the mass, cortical Dp,radial was significantly higher than in controls (P = 0.012). Conversely, medullary Dp,axial was significantly lower in contralateral than ipsilateral kidneys (P = 0.027) and normal controls (P = 0.044). DATA CONCLUSION: REFMAP-MRI parameters provide unique information regarding renal dysfunction. In presurgical renal mass patients, directional flow changes were noted that were not identified with IVIM analysis alone. Both contralateral and ipsilateral kidneys in patients show reductions in structural diffusivities and anisotropy, while flow metrics showed opposing changes in contralateral vs. ipsilateral kidneys. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Comparison between qualitative and quantitative assessment of background parenchymal enhancement on breast MRI.

BACKGROUND: Potential clinical implications of the level of background parenchymal enhancement (BPE) on breast MRI are increasing. Currently, BPE is typically evaluated subjectively. Tests of concordance between subjective BPE assessment and computer-assisted quantified BPE have not been reported. PURPOSE OR HYPOTHESIS: To compare subjective radiologist assessment of BPE with objective quantified parenchymal enhancement (QPE). STUDY TYPE: Cross-sectional observational study. POPULATION: Between 7/24/2015 and 11/27/2015, 104 sequential patients (ages 23 - 81 years, mean 49 years) without breast cancer underwent breast MRI and were included in this study. FIELD STRENGTH/SEQUENCE: 3T; fat suppressed axial T2, axial T1, and axial fat suppressed T1 before and after intravenous contrast. ASSESSMENT: Four breast imagers graded BPE at 90 and 180 s after contrast injection on a 4-point scale (a-d). Fibroglandular tissue masks were generated using a phantom-validated segmentation algorithm, and were co-registered to pre- and postcontrast fat suppressed images to define the region of interest. QPE was calculated. STATISTICAL TESTS: Receiver operating characteristic (ROC) analyses and kappa coefficients (k) were used to compare subjective BPE with QPE. RESULTS: ROC analyses indicated that subjective BPE at 90 s was best predicted by quantified QPE ≤20.2 = a, 20.3-25.2 = b, 25.3-50.0 = c, >50.0 = d, and at 180 s by quantified QPE ≤ 32.2 = a, 32.3-38.3 = b, 38.4-74.5 = c, >74.5 = d. Agreement between subjective BPE and QPE was slight to fair at 90 s (k = 0.20-0.36) and 180 s (k = 0.19-0.28). At higher levels of QPE, agreement between subjective BPE and QPE significantly decreased for all four radiologists at 90 s (P ≤ 0.004) and for three of four radiologists at 180 s (P ≤ 0.004). DATA CONCLUSION: Radiologists were less consistent with QPE as QPE increased. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1685-1691.

Voxelwise analysis of simultaneously acquired and spatially correlated 18 F-fluorodeoxyglucose (FDG)-PET and intravoxel incoherent motion metrics in breast cancer.

PURPOSE: Diffusion-weighted imaging (DWI) and 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET) independently correlate with malignancy in breast cancer, but the relationship between their structural and metabolic metrics is not completely understood. This study spatially correlates diffusion, perfusion, and glucose avidity in breast cancer with simultaneous PET/MR imaging and compares correlations with clinical prognostics. METHODS: In this Health Insurance Portability and Accountability Act-compliant prospective study, with written informed consent and approval of the institutional review board and using simultaneously acquired FDG-PET and DWI, tissue diffusion (Dt ), and perfusion fraction (fp ) from intravoxel incoherent motion (IVIM) analysis were registered to FDG-PET within 14 locally advanced breast cancers. Lesions were analyzed using 2D histograms and correlation coefficients between Dt , fp , and standardized uptake value (SUV). Correlations were compared with prognostics from biopsy, metastatic burden from whole-body PET, and treatment history. RESULTS: SUV||Dt correlation coefficient significantly distinguished treated (0.11 ± 0.24) from nontreated (-0.33 ± 0.26) patients (P = 0.005). SUV||fp correlations were on average negative for the whole cohort (-0.17 ± 0.13). CONCLUSION: Simultaneously acquired and registered FDG-PET/DWI allowed quantifiable descriptions of breast cancer microenvironments that may provide a framework for monitoring and predicting response to treatment. Magn Reson Med 78:1147-1156, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Lung Adenocarcinoma: Correlation of Quantitative CT Findings with Pathologic Findings.

Purpose To identify the ability of computer-derived three-dimensional (3D) computed tomographic (CT) segmentation techniques to help differentiate lung adenocarcinoma subtypes. Materials and Methods This study had institutional research board approval and was HIPAA compliant. Pathologically classified resected lung adenocarcinomas (n = 41) with thin-section CT data were identified. Two readers independently placed over-inclusive volumes around nodules from which automated computer measurements were generated: mass (total mass) and volume (total volume) of the nodule and of any solid portion, in addition to the solid percentage of the nodule volume (percentage solid volume) or mass (percentage solid mass). Interobserver agreement and differences in measurements among pathologic entities were evaluated by using t tests. A multinomial logistic regression model was used to differentiate the probability of three diagnoses: invasive non-lepidic-predominant adenocarcinoma (INV), lepidic-predominant adenocarcinoma (LPA), and adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA). Results Mean percentage solid volume of INV was 35.4% (95% confidence interval [CI]: 26.2%, 44.5%)-higher than the 14.5% (95% CI: 10.3%, 18.7%) for LPA (P = .002). Mean percentage solid volume of AIS/MIA was 8.2% (95% CI: 2.7%, 13.7%) and had a trend toward being lower than that for LPA (P = .051). Accuracy of the model based on total volume and percentage solid volume was 73.2%; accuracy of the model based on total mass and percentage solid mass was 75.6%. Conclusion Computer-assisted 3D measurement of nodules at CT had good reproducibility and helped differentiate among subtypes of lung adenocarcinoma. (©) RSNA, 2016.