Dynamic Contrast-enhanced Parameters Research Articles

Improved diagnostic confidence and tumor type prediction in adult-type diffuse glioma by multimodal imaging including DCE perfusion and diffusion kurtosis mapping – A standardized multicenter study

Background and purposeTo evaluate the feasibility of a multimodal approach involving dynamic contrast-enhanced (DCE) perfusion imaging and diffusion kurtosis imaging (DKI) in the preoperative imaging of brain tumors in a multicenter setting, and to evaluate the effect on diagnostic confidence and accuracy for tumor grade and type prediction. Materials and MethodsOne hundred and thirty-three patients with brain tumors were imaged in six hospitals with a standardized multimodal protocol. Standard imaging and six parameter maps derived from DCE and DKI sequences were reviewed off-site by two independent readers. Image quality and diagnostic confidence were evaluated in qualitative analyses. Quantitative analyses were performed to assess diagnostic accuracy and the performance of DKI and DCE parameters for tumor grade differentiation and molecular tumor type determination. ResultsStandardized acquisition of DCE and DKI maps was feasible with excellent image quality. Diagnostic confidence was significantly improved from 85 % to 96 % (p = 0.0005) by additional review of the DCE and DKI maps. The combination of mean kurtosis and CBV was particularly advantageous for differentiating low-grade and high-grade glioma, oligodendroglial vs. astrocytic, and IDH1/2 wild type vs. mutated tumors. ConclusionA multimodal imaging approach with DCE and DKI improves diagnostic confidence and yields higher diagnostic accuracy for predicting tumor grade and type in adult-type glioma.

Dynamic Contrast Enhanced MRI as a Biomarker of Tumor Response and Oncologic Outcomes in Head and Neck Cancer: Results of a Single Institution Prospective Imaging Study

We aim to determine the correlation between vascular parameters of Dynamic contrast enhanced (DCE) MRIs and tumor response and outcomes in head and neck (HNC) patients treated with definitive radiation therapy (RT). Eighty-two HNC patients are included in this prospective study in one institute. All patients had malignant head and neck neoplasm indicative of curative- intent treatment. Patients were imaged using MRIs pre-, mid-, and post-RT completion at 8-12 weeks. T2-weighted sequences were used for tumor contouring then it was co-registered to respective DCE images. The response to treatment was checked at mid-radiotherapy (mid-RT) and at the end of RT. Mid-RT MRI was co-registered to baseline images and the manually segmented baseline primary tumor regions of interest were propagated to mid-RT images. Quantitative maps (Ktrans, Kep, Ve and Vp) were generated with the extended Tofts pharmacokinetic models and were used for analysis. These vascular parameters were presented as a mean value and percentile using histogram analysis and the following parameters were extracted using an in-house programming environment script: mean, 5th, 10th, 20th, 30th, 40th, 50th (i.e., median), 60th, 70th, 80th, 90th, 95th percentile. The non-parametric Wilcoxon signed-rank test was used to assess the changes of mid-RT DCE parameters compared to baseline. Recursive partitioning analysis (RPA) was used to identify the delta DCE threshold associated with relapse. We assessed the identified thresholds' correlation with oncological and survival endpoints using Cox regression with and without standard clinical variables. The median age for patients is 61 years old (33-78 range). Never smokers are 39 (47%), 35 (43%) are former smoker and 8 (10%) are current smoker with a mean value of 14 pack per year and 26 standard deviations. Using AJCC 8th edition, 39 (47%) are stage I and 19 (23%) are stage II and stage III and IV are 15 (18%) and 9 (10%) respectively. HPV positive are 72 (88%). For patients with GTV-P at baseline (n = 60), 11 (18%) had mid-RT CR at the primary site which increased to 50 (83%) post-RT. The LC and RFS for the entire cohort were 91.4%, and 79.2% respectively. In GTV-P, none of the pre-radiotherapy DCE parameters were correlated with LC or RFS. Wilcoxon signed rank test was statistically significant in 80, 90 and 95 percentiles with (p<0.05). RPA analysis identified different thresholds for each DCE parameter, and its inclusions to the multivariate model improved its performance. In GTV-P, RPA analysis identified ΔKtrans 40 percentiles >15.6% at mid-RT as the most significant point. When this value of ΔKtrans added to the multivariate analysis it was associated with a significantly better model performance in RFS (p = 0.00001). DCE parameters are a very promising tool to correlate with response and outcomes in H&N cancer patients. Future work is warranted for external validation of our findings.

Assessment of Dynamic Contrast Enhanced (DCE) MRI for Detection of Radiotherapy Induced Alteration in Mandibular Vasculature

We aim to determine the kinetics of DCE-MRI changes in various mandibular risk volumes based on radiation (RT) dose received. Eighty-eight head and neck cancer (HNC) patients (Pts) who underwent definitive RT were enrolled in this prospective study after IRB approval and informed consent. Images were acquired at pre-RT (Baseline), 3 weeks after RT start date (Mid-RT), 3 mos post-RT (PostRT1), and 6 mos post-RT (PostRT2). Manually segmented mandibular volumes on T2-weighted images were propagated to co-registered DCE-MRIs. Planning CTs and dose grids were also co-registered to corresponding baseline T2 images to create 3-D dose subvolumes. These were used to create 3 risk subvolumes; <30 Gy, 30-50 Gy, and >50 Gy ROIs. DCE images of different timepoints (TPs) were deformably co-registered and the dose subvolumes were propagated to each TP. We used the extended-Tofts model to generate the vascular quantitative maps (Ktrans and Ve). Each subvolume histogram parameters were extracted at each TP. Wilcoxon Signed Rank test was used to compare the changes at different TPs compared to baseline. We classified Pts' delta parameters at different TPs -based on our prior extensive QA assessment- into Pts with stable vascular profile (±25% change), Pts with significant increase (>25% change) and Pts with significant decrease (<-25%). Chi-square test was used to assess the change at different TPs. For <30 Gy subvolumes, there were no significant changes (p > 0.05) in the studied DCE parameters at all TPs except a significant decrease (p < 0.001) in median Ktrans at PostRT2. For 30-50 Gy subvolumes, there was a significant increase in median Ktrans that started at MidRT (p = 0.006) and continued at PostRT1 (p = 0.04) but recovered to baseline values at PostRT2. Median Ve on the other hand only showed significant increase at PostRT1 (p = 0.001), but other TPs were not significantly different compared to baseline. Similarly, subvolumes >50 Gy showed same kinetics as in 30-50 Gy with significant increase of Ktrans at MidRT and PostRT1 and significant increase in Ve in only PostRT1 (P <0.05). For <30 Gy, there was significant increase in the number of Pts with stable or decrease in Ktrans at PostRT2 compared to earlier TPs (70% vs. 60% at PostRT1 and 54% at MidRT p = 0.003). 30-50 Gy subvolumes showed similar profile like <30 Gy with significant increase in the percentage of Pts with recovery at PostRT2. However, for >50 Gy, there was no significant increase in the number of Pts who recovered at PostRT2 (p = 0.3). Ve showed no significant increase in the percentage of Pts with recovery at different TPs (p > 0.05). Results showed that for all dose mandibular subvolumes, there is an acute vascular insult that tends to recover at +6 months post-RT except for a selective group of patients who continue to have persistence of the vascular insult at high dose subvolumes. These findings are of importance for future selection of high risk population for prophylactic intervention against osteoradionecrosis.

Diagnostic efficacy of diffusion-weighted imaging and semiquantitative and quantitative dynamic contrast-enhanced magnetic resonance imaging in salivary gland tumors.

Increased use of functional magnetic resonance imaging (MRI) methods such as diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI consisting of sequential contrast series, allows us to obtain more information on the microstructure, cellularity, interstitial distance, and vascularity of tumors, which has increased the discrimination power for benign and malignant salivary gland tumors (SGTs). In the last few years, quantitative DCE MRI data containing T1 perfusion parameters (Ktrans, Kep and Ve), were reported to contribute to the differentiation of benign or malignant subtypes in SGTs. To evaluate the diagnostic efficacy of DWI and semiquantitative and quantitative perfusion MRI parameters in SGTs. Diffusion MRI [apparent diffusion coefficient (ADC) value] with a 1.5 T MR machine, semiquantitative perfusion MRI [time intensity curve (TIC) pattern], and quantitative perfusion MRI examinations (Ktrans, Kep and Ve) of 73 tumors in 67 patients with histopathological diagnosis performed from 2017 to 2021 were retrospectively evaluated. In the ADC value and semiquantitative perfusion MRI measurements, cystic components of the tumors were not considered, and the region of interest (ROI) was manually placed through the widest axial section of the tumor. TIC patterns were divided into four groups: Type A = Tpeak > 120 s; type B = Tpeak ≤ 120 s, washout ratio (WR) ≥ 30%; type C = Tpeak ≤ 120 s, WR < 30%; and type D = flat TIC. For the quantitative perfusion MRI analysis, a 3D ROI was placed in the largest solid component of the tumor, and the Ktrans, Kep and Ve values were automatically generated. The majority of SGTs were located in the parotid glands (86.3%). Of all the SGTs, 68.5% were benign and 31.5% were malignant. Significant differences were found for ADC values among pleomorphic adenomas (PMAs), Warthin's tumors (WTs), and malignant tumors (MTs) (P < 0.001). PMAs had type A and WTs had type B TIC pattern while the vast majority of MTs and other benign tumors (OBTs) (54.5% and 45.5%, respectively) displayed type C TIC pattern. PMAs showed no washout, while the highest mean WR was observed in WTs (59% ± 11%). Ktrans values of PMAs, WTs, OBTs, and MTs were not significantly different. Kep values of PMAs and WTs were significantly different from those of OBTs and MTs. Mean Ve value of WTs was significantly different from those of PMAs, OBTs, and MTs (P < 0.001). The use of quantitative DCE parameters along with diffusion MRI and semiquantitative contrast-enhanced MRI in SGTs could improve the diagnostic accuracy.

Semi-quantitative and quantitative dynamic contrast-enhanced (DCE) MRI parameters as prostate cancer imaging biomarkers for biologically targeted radiation therapy

BackgroundBiologically targeted radiation therapy treatment planning requires voxel-wise characterisation of tumours. Dynamic contrast enhanced (DCE) DCE MRI has shown promise in defining voxel-level biological characteristics. In this study we consider the relative value of qualitative, semi-quantitative and quantitative assessment of DCE MRI compared with diffusion weighted imaging (DWI) and T2-weighted (T2w) imaging to detect prostate cancer at the voxel level.MethodsSeventy prostate cancer patients had multiparametric MRI prior to radical prostatectomy, including T2w, DWI and DCE MRI. Apparent Diffusion Coefficient (ADC) maps were computed from DWI, and semi-quantitative and quantitative parameters computed from DCE MRI. Tumour location and grade were validated with co-registered whole mount histology. Kolmogorov–Smirnov tests were applied to determine whether MRI parameters in tumour and benign voxels were significantly different. Cohen’s d was computed to quantify the most promising biomarkers. The Parker and Weinmann Arterial Input Functions (AIF) were compared for their ability to best discriminate between tumour and benign tissue. Classifier models were used to determine whether DCE MRI parameters improved tumour detection versus ADC and T2w alone.ResultsAll MRI parameters had significantly different data distributions in tumour and benign voxels. For low grade tumours, semi-quantitative DCE MRI parameter time-to-peak (TTP) was the most discriminating and outperformed ADC. For high grade tumours, ADC was the most discriminating followed by DCE MRI parameters Ktrans, the initial rate of enhancement (IRE), then TTP. Quantitative parameters utilising the Parker AIF better distinguished tumour and benign voxel values than the Weinmann AIF. Classifier models including DCE parameters versus T2w and ADC alone, gave detection accuracies of 78% versus 58% for low grade tumours and 85% versus 72% for high grade tumours.ConclusionsIncorporating DCE MRI parameters with DWI and T2w gives improved accuracy for tumour detection at a voxel level. DCE MRI parameters should be used to spatially characterise tumour biology for biologically targeted radiation therapy treatment planning.

Diffusion Tensor and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlate with Molecular Markers of Inflammation in the Synovium.

It is difficult to capture the severity of synovial inflammation on imaging. Herein we hypothesize that diffusion tensor imaging (DTI) derived metrics may delineate the aggregation of the inflammatory cells and expression of inflammatory cytokines and dynamic contrast-enhanced (DCE) imaging may provide information regarding vascularity in the inflamed synovium. Patients with knee arthritis (&gt;3-months duration) underwent conventional (T2-weighted fast spin echo and spin echo T1-weighted images) as well as DTI and DCE MRI and thereafter arthroscopic guided synovial biopsy. DCE and DTI metrics were extracted from the masks of the segments of the inflamed synovium which enhanced on post-contrast T1-weighted MRI. These metrics were correlated with immunohistochemistry (IHC) parameters of inflammation on synovium. Pearson's correlation was performed to study the relationship between DTI- and DCE-derived metrics, IHC parameters, and post-contrast signal intensity. Linear regression model was used to predict the values of IHC parameters using various DTI and DCE derived metrics as predictors. There were 80 patients (52 male) with mean age 39.78 years and mean disease duration 19.82 months. Nineteen patients had tuberculosis and the rest had chronic undifferentiated monoarthritis (n = 31), undifferentiated spondyloarthropathy (n = 14), rheumatoid arthritis (n = 6), osteoarthritis (n = 4), reactive arthritis (n = 3), ankylosing spondylitis (n = 2), and juvenile idiopathic arthritis (n = 1). Fractional anisotropy (FA), a metric of DTI, had significant correlation with number of immune cells (r = 0.87, p &lt; 0.01) infiltrating into the synovium and cytokines (IL-1β, r = 0.55, p &lt; 0.01; TNF-α, r = 0.42, p &lt; 0.01) in all patients and also in each group of patients and adhesion molecule expressed on these cells in all patients (CD54, r = 0.51, p &lt; 0.01). DCE parameters significantly correlated with CD34 (blood flow, r = 0.78, p &lt; 0.01; blood volume, r = 0.76, p &lt; 0.01) in each group of patients, a marker of neo-angiogenesis. FA was the best predictor of infiltrating inflammatory cells, adhesion molecule and proinflammatory cytokines. Amongst the DCE parameters, blood volume, was best predictor of CD34. DTI and DCE metrics capture cellular and molecular markers of synovial inflammation in patients with chronic inflammatory arthritis.

Evaluation of tracer kinetic parameters in cervical cancer using dynamic contrast-enhanced MRI as biomarkers in terms of biological relevance, diagnostic performance and inter-center variability.

This study assessed the clinical value of parameters derived from dynamic contrast-enhanced (DCE) MRI with respect to correlation with angiogenesis and proliferation of cervical cancer, performance of diagnosis and reproducibility of DCE-MRI parameters across MRI scanners. A total of 113 patients with cervical carcinoma from two centers were included in this retrospective study. The DCE data were centralized and processed using five tracer kinetic models (TKMs) (Tofts, Ex-Tofts, ATH, SC, and DP), yielding the following parameters: volume transfer constant (Ktrans), extravascular extracellular volume (Ve), fractional volume of vascular space (Vp), blood flow (Fp), and permeability surface area product (PS). CD34 counts and Ki-67 PI (proliferation index) of cervical cancer and normal cervix tissue were obtained using immunohistochemical staining in Center 1. CD34 count and Ki-67 PI in cervical cancer were significantly higher than in normal cervix tissue (p<0.05). Parameter Ve from each TKM was significantly smaller in cervical cancer tissue than in normal cervix tissue (p<0.05), indicating the higher proliferation of cervical cancer cells. Ve of each TKM attained the largest AUC to diagnose cervical cancer. The distributions of DCE parameters for both cervical cancer and normal cervix tissue were not significantly different between two centers (P>0.05). Parameter Ve was similar to the expression of Ki-67 in revealing the proliferation of tissue cells, attained good performance in diagnosis of cervical cancer, and demonstrated consistent findings on measured values across centers.

Dynamic Contrast-Enhanced MRI in the Abdomen of Mice with High Temporal and Spatial Resolution Using Stack-of-Stars Sampling and KWIC Reconstruction.

Application of quantitative dynamic contrast-enhanced (DCE) MRI in mouse models of abdominal cancer is challenging due to the effects of RF inhomogeneity, image corruption from rapid respiratory motion and the need for high spatial and temporal resolutions. Here we demonstrate a DCE protocol optimized for such applications. The method consists of three acquisitions: (1) actual flip-angle B1 mapping, (2) variable flip-angle T1 mapping and (3) acquisition of the DCE series using a motion-robust radial strategy with k-space weighted image contrast (KWIC) reconstruction. All three acquisitions employ spoiled radial imaging with stack-of-stars sampling (SoS) and golden-angle increments between the views. This scheme is shown to minimize artifacts due to respiratory motion while simultaneously facilitating view-sharing image reconstruction for the dynamic series. The method is demonstrated in a genetically engineered mouse model of pancreatic ductal adenocarcinoma and yielded mean perfusion parameters of Ktrans = 0.23 ± 0.14 min−1 and ve = 0.31 ± 0.17 (n = 22) over a wide range of tumor sizes. The SoS-sampled DCE method is shown to produce artifact-free images with good SNR leading to robust estimation of DCE parameters.

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.

Longitudinal Correlations Between Intravoxel Incoherent Motion (IVIM) and Dynamic Contrast-Enhanced (DCE) MRI During Radiotherapy in Prostate Cancer Patients.

PurposeIntravoxel incoherent motion (IVIM) is a promising technique that can acquire perfusion information without the use of contrast agent, contrary to the more established dynamic contrast-enhanced (DCE) technique. This is of interest for treatment response monitoring, where patients can be imaged on each treatment fraction. In this study, longitudinal correlations between IVIM- and DCE parameters were assessed in prostate cancer patients receiving radiation treatment.Materials and Methods20 prostate cancer patients were treated on a 1.5 T MR-linac with 20 x 3 or 3.1 Gy. Weekly IVIM and DCE scans were acquired. Tumors, the peripheral zone (PZ), and the transition zone (TZ) were delineated on a T2-weighted scan acquired on the first fraction. IVIM and DCE scans were registered to this scan and the delineations were propagated. Median values from these delineations were used for further analysis. The IVIM parameters D, f, D* and the product fD* were calculated. The Tofts model was used to calculate the DCE parameters Ktrans, kep and ve. Pearson correlations were calculated for the IVIM and DCE parameters on values from the first fraction for each region of interest (ROI). For longitudinal analysis, the repeated measures correlation coefficient was used to determine correlations between IVIM and DCE parameters in each ROI.ResultsWhen averaging over patients, an increase during treatment in all IVIM and DCE parameters was observed in all ROIs, except for D in the PZ and TZ. No significant Pearson correlations were found between any pair of IVIM and DCE parameters measured on the first fraction. Significant but low longitudinal correlations were found for some combinations of IVIM and DCE parameters in the PZ and TZ, while no significant longitudinal correlations were found in the tumor. Notably in the TZ, for both f and fD*, significant longitudinal correlations with all DCE parameters were found.ConclusionsThe increase in IVIM- and DCE parameters when averaging over patients indicates a measurable response to radiation treatment with both techniques. Although low, significant longitudinal correlations were found which suggests that IVIM could potentially be used as an alternative to DCE for treatment response monitoring.

Dynamic contrast-enhanced MRI in malignant pleural mesothelioma: prediction of outcome based on DCE-MRI measurements in patients undergoing cytotoxic chemotherapy

BackgroundThe malignant pleural mesothelioma (MPM) response rate to chemotherapy is low. The identification of imaging biomarkers that could help guide the most effective therapy approach for individual patients is highly desirable. Our aim was to investigate the dynamic contrast-enhanced (DCE) MR parameters as predictors for progression-free (PFS) and overall survival (OS) in patients with MPM treated with cisplatin-based chemotherapy.MethodsThirty-two consecutive patients with MPM were enrolled in this prospective study. Pretreatment and intratreatment DCE-MRI were scheduled in each patient. The DCE parameters were analyzed using the extended Tofts (ET) and the adiabatic approximation tissue homogeneity (AATH) model. Comparison analysis, logistic regression and ROC analysis were used to identify the predictors for the patient’s outcome.ResultsPatients with higher pretreatment ET and AATH-calculated Ktrans and ve values had longer OS (P≤.006). Patients with a more prominent reduction in ET-calculated Ktrans and kep values during the early phase of chemotherapy had longer PFS (P =.008). No parameter was identified to predict PFS. Pre-treatment ET-calculated Ktrans was found to be an independent predictive marker for longer OS (P=.02) demonstrating the most favourable discrimination performance compared to other DCE parameters with an estimated sensitivity of 89% and specificity of 78% (AUC 0.9, 95% CI 0.74-0.98, cut off > 0.08 min-1).ConclusionsIn the present study, higher pre-treatment ET-calculated Ktrans values were associated with longer OS. The results suggest that DCE-MRI might provide additional information for identifying MPM patients that may respond to chemotherapy.

Apparent Diffusion Coefficient Values and Dynamic Contrast-Enhanced Magnetic Resonance Perfusion are Potential Predictors for Grading Meningiomas.

Purpose: Distinguishing between high-grade and low-grade meningiomas might be difficult but has high clinical value in deciding precise treatment and prognostic factors. Magnetic resonance imaging (MRI) using apparent diffusion coefficient (ADC) values and dynamic contrast enhancement (DCE) may have a significant role in capturing such complexities.Methods: Data from our hospital database on meningioma patients from January 2020 to December 2021 were obtained. The MRI results of all patients were evaluated for mean ADC value and DCE parameters, including time-signal intensity curves (TIC), maximum signal intensity (SImax), time to maximum signal intensity (Tmax), maximum contrast enhancement ratio (MCER), and slope.Results: In this retrospective analysis, 33 individuals were included. Twenty-eight (84.8%) patients were pathologically diagnosed with low-grade meningioma and five (15.2%) patients with high-grade meningioma. There is a crossover between high- and low-grade meningiomas in conventional MRI. Tumor size, location, shape, necrotic/cystic changes, peritumoral edema, and enhancement patterns did not differ substantially between groups (p = 0.39, 0.23, 0.28, 0.57, 0.56, and 0.33, respectively). The mean ADC and Tmax values of high-grade meningiomas were substantially lower than those of low-grade meningiomas (p = 0.002 and 0.02, respectively). An optimal cut-off of 0.87 × 10-3 mm2s-1 for the mean ADC value (area under the curve [AUC] = 0.94, sensitivity = 80%, specificity = 92.8%) and 42 s for Tmax (AUC = 0.84, sensitivity = 80%, specificity = 89.3%) was suggested. High-grade meningiomas had significantly higher TIC, SImax, MCER, and slope than low-grade meningiomas (p = 0.004, < 0.001, 0.01, and 0.001, respectively). Type IV TIC had a sensitivity of 80% and specificity of 89.3% in distinguishing high-grade meningiomas from low-grade meningiomas. Optimal cut-offs of 940.2 for SImax (AUC = 0.98, sensitivity = 80%, specificity = 96.4%), 245% for MCER (AUC = 0.94, sensitivity = 80%, specificity = 85.7%), and 5% per second for slope (AUC = 0.97, sensitivity = 80%, specificity = 96.4%) were estimated.Conclusion: The ADC value and DCE-MRI parameters (TIC, SImax, Tmax, MCER, and slope) are potential predictors for separating high-grade from low-grade meningiomas.

Dynamic contrast-enhanced magnetic resonance perfusion volumetrics can differentiate tuberculosis of the spine and vertebral malignancy

There is considerable overlap in radiologic features of tubercular and malignant spinal lesions on conventional magnetic resonance imaging (MRI). To evaluate the role of dynamic contrast-enhanced (DCE) MRI perfusion parameters in differentiating vertebral malignancy from spinal tuberculosis. This was a prospective study and we enrolled consecutive patients presenting with a clinical/radiologic evidence of vertebral lesions. DCE-MRI of the spine was performed using 3D volume interpolated breath-hold examination (VIBE) sequence after intravenously injecting 0.1 mmol/kg body weight of gadopentetate dimeglumine. We used Tofts model to calculate DCE parameters that included Ktrans (transfer constant), kep (rate constant), ve (fractional volume of extracellular extravascular space), and iAUC (initial area under the curve). We compared the mean value of each perfusion parameter by type of lesion (tubercular/malignant) at 0.05 significance level and performed receiver operating characteristic curve analysis. We could confirm histologic/cytologic diagnosis in 35 of the 45 patients recruited. Of these, 19 were tubercular and 16 were malignant lesions. The mean (± standard deviation) of kep (min-1) was significantly higher (2.89 ± 3.3) in malignant compared to tubercular lesions (0.81 ± 0.19), whereas ve was significantly lower in malignant (0.27 ± 0.13 mL/g) compared to benign lesions (0.47 ± 0.12 mL/g) at 0.05 significance level. kep cutoff of ≥1.17 min-1 had a sensitivity of 93.8% and specificity of 100% with a diagnostic accuracy of 94.4% in detecting malignant disease. High kep is the single best predictor of malignant vertebral lesions. We recommend kep cutoff value of ≥1.17 min-1 that has high diagnostic accuracy in identifying malignant lesions.

Predictive Value of Multiparametric MRI for Response to Single-Cycle Induction Chemo-Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma.

ObjectivesTo assess the predictive value of multiparametric MRI for treatment response evaluation of induction chemo-immunotherapy in locally advanced head and neck squamous cell carcinoma.MethodsTwenty-two patients with locally advanced, histologically confirmed head and neck squamous cell carcinoma who were enrolled in the prospective multicenter phase II CheckRad-CD8 trial were included in the current analysis. In this unplanned secondary single-center analysis, all patients who received contrast-enhanced MRI at baseline and in week 4 after single-cycle induction therapy with cisplatin/docetaxel combined with the immune checkpoint inhibitors tremelimumab and durvalumab were included. In week 4, endoscopy with representative re-biopsy was performed to assess tumor response. All lesions were segmented in the baseline and restaging multiparametric MRI, including the primary tumor and lymph node metastases. The volume of interest of the respective lesions was volumetrically measured, and time-resolved mean intensities of the golden-angle radial sparse parallel-volume-interpolated gradient-echo perfusion (GRASP-VIBE) sequence were extracted. Additional quantitative parameters including the T1 ratio, short-TI inversion recovery ratio, apparent diffusion coefficient, and dynamic contrast-enhanced (DCE) values were measured. A model based on parallel random forests incorporating the MRI parameters from the baseline MRI was used to predict tumor response to therapy. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic performance.ResultsFifteen patients (68.2%) showed pathologic complete response in the re-biopsy, while seven patients had a residual tumor (31.8%). In all patients, the MRI-based primary tumor volume was significantly lower after treatment. The baseline DCE parameters of time to peak and wash-out were significantly different between the pathologic complete response group and the residual tumor group (p < 0.05). The developed model, based on parallel random forests and DCE parameters, was able to predict therapy response with a sensitivity of 78.7% (95% CI 71.24–84.93) and a specificity of 78.6% (95% CI 67.13–87.48). The model had an area under the ROC curve of 0.866 (95% CI 0.819–0.914).ConclusionsDCE parameters indicated treatment response at follow-up, and a random forest machine learning algorithm based on DCE parameters was able to predict treatment response to induction chemo-immunotherapy.

Usefulness of Arterial Spin Labeling-Tumor Blood Flow and Dynamic Contrast-Enhanced Perfusion Techniques in Predicting Treatment Response of Nasopharyngeal Carcinoma

OBJECTIVES: To demonstrate the usefulness of arterial spin labeling (ASL)- tumor blood flow (TBF) and dynamic contrast enhancement (DCE) parameters in predicting the treatment response in patients with nasopharyngeal carcinoma (NPC) after 3-months of radiotherapy. MATERIALS AND METHODS: Ten NPC patients who underwent magnetic resonance imaging (MRI) examinations with both ASL-TBF and DCE techniques before treatment and at the 3-month follow-up after radiotherapy were divided into complete-response (CR) and partial-response (PR) groups according to the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1. The ASL-TBF and DCE parameters of the nasopharynx comprised TBF, Ktrans, IAUGC, Kep, and Ve were analyzed and compared between the two groups. RESULTS: The CR group had a significantly higher pre-treatment Ve ratio (p = 0.038), a higher post-treatment TBF value (p = 0.038), and a higher post-treatment K trans value (p = 0.067) than the PR group. CONCLUSION: The ASL-TBF and DCE techniques might be useful tools for the prediction of the treatment responses 3-months after radiotherapy in patients with NPC.

Differentiation between glioblastoma and primary CNS lymphoma: application of DCE-MRI parameters based on arterial input function obtained from DSC-MRI.

This study aimed to evaluate whether arterial input functions (AIFs) obtained from dynamic susceptibility contrast (DSC)-MRI (AIFDSC) improve the reliability and diagnostic accuracy of dynamic contrast-enhanced (DCE)-derived pharmacokinetic (PK) parameters for differentiating glioblastoma from primary CNS lymphoma (PCNSL) compared with AIFs derived from DCE-MRI (AIFDCE). This retrospective study included 172 patients with glioblastoma (n = 147) and PCNSL (n = 25). All patients had undergone preoperative DSC- and DCE-MRI. The volume transfer constant (Ktrans), volume of the vascular plasma space (vp), and volume of the extravascular extracellular space (ve) were acquired using AIFDSC and AIFDCE. The relative cerebral blood volume (rCBV) was obtained from DSC-MRI. Intraclass correlation coefficients (ICC) and ROC curves were used to assess the reliability and diagnostic accuracy of individual parameters. The mean Ktrans, vp, and ve values revealed better ICCs with AIFDSC than with AIFDCE (Ktrans, 0.911 vs 0.355; vp, 0.766 vs 0.503; ve, 0.758 vs 0.657, respectively). For differentiating all glioblastomas from PCNSL, the mean rCBV (AUC = 0.856) was more accurate than the AIFDSC-driven mean Ktrans, which had the largest AUC (0.711) among the DCE-derived parameters (p = 0.02). However, for glioblastomas with low rCBV (≤ 75th percentile of PCNSL; n = 30), the AIFDSC-driven mean Ktrans and vp were more accurate than rCBV (AUC: Ktrans, 0.807 vs rCBV, 0.515, p = 0.004; vp, 0.715 vs rCBV, p = 0.045). DCE-derived PK parameters using the AIFDSC showed improved reliability and diagnostic accuracy for differentiating glioblastoma with low rCBV from PCNSL. • An accurate differential diagnosis of glioblastoma and PCNSL is crucial because of different therapeutic strategies. • In contrast to the rCBV from DSC-MRI, another perfusion imaging technique, the DCE parameters for the differential diagnosis have been limited because of the low reliability of AIFs from DCE-MRI. • When we analyzed DCE-MRI data using AIFs from DSC-MRI (AIFDSC), AIFDSC-driven DCE parameters showed improved reliability and better diagnostic accuracy than rCBV for differentiating glioblastoma with low rCBV from PCNSL.

Hypoperfusion of the infrapatellar fat pad and its relationship to MRI T2* relaxation time changes in a 5/6 nephrectomy model

The purpose of present study was to longitudinally investigate the alterations in infrapatellar fat pad (IPFP) vascularity in 5/6 nephrectomized rats by using dynamic contrast enhanced (DCE) MRI and IPFP degeneration by using MRI T2* relaxation time. Twelve male Sprague–Dawley rats were assigned to a control group and a 5/6 nephrectomy CKD group. The right knees of all rats were longitudinally scanned by 4.7 T MRI, and serial changes in the IPFP were assessed at 0, 8, 16, 30, and 44 weeks by DCE-MRI (parameters A, kel and kep) and MRI T2* mapping. After MRI measurements, knee specimens were obtained and evaluated histologically. The CKD group had IPFPs with lower blood volume A and lower permeability kep values from 16 weeks (p < 0.05), lower venous washout kel value from 30 weeks (p < 0.001), and significantly higher T2* values reflecting adipocyte degeneration beginning at 16 weeks (p < 0.05). The histopathological results confirmed the MRI findings. Hypoperfusion and adipocytes degeneration related to CKD were demonstrated in a rodent 5/6 nephrectomy model. DCE parameters and MRI T2* can serve as imaging biomarkers of fat pad degeneration during CKD progression.

Is quantitative DCE-MRI useful in differentiation of indolent and significant prostate cancers?

Aim: Direct visual assessment is recommended in prostate magnetic resonance imaging (MRI) for dynamic contrast enhancement (DCE), however, being a qualitative approach, it may cause inter-reader variability. The purpose of this study was to compare quantitative DCE parameters in the differentiation of clinically significant prostate cancer from indolent cancer using whole-mount histopathology. Methods: Seventy-six patients who underwent multiparametric MRI with suspicion of prostate cancer and subsequent radical prostatectomy were included. Index tumor location was determined with pathology reports. MRI findings of this location were evaluated by a different radiologist using prostate imaging-reporting and data system version 2.1 (PI-RADSv2.1) guideline. Gleason 3+3 tumors were considered indolent, and Gleason ≥ 3+4 tumors were considered significant cancers. Region-of-interests (ROI) were placed in the lesion and the normal peripheral zone. Lesion values and lesion/normal ratios of Ktrans, Kep, Ve, area under curve (iAUC) were calculated. T test was used in statistical analysis. Results: The numbers of cases with PI-RADSv2.1 scores of 2, 3, 4 and 5 were 5, 4, 24, and 43, respectively. There were 13 indolent cases and 63 patients with significant prostate cancer. Lesion/normal ratios of Ktrans, Kep, Ve, iAUC were 1.6, 1.59, 12, 2.1, respectively, in indolent cancers, and 3.1, 4.04, 1.39, 2.8, respectively, in significant cancers. Lesion/normal ratio of Ktrans was higher in significant cancers while lesion/normal ratio of Ve was higher in indolent cancers. Kep and iAUC were similar (P>0.05 for each). Conclusion: Quantitative DCE assessment may demonstrate more reproducible results. Lesion/normal tissue ratios of Ktrans and Ve were helpful in differentiation between indolent and significant prostate cancers.

Differentiation of recurrent diffuse glioma from treatment-induced change using amide proton transfer imaging: incremental value to diffusion and perfusion parameters.

To evaluate the incremental value of amide proton transfer (APT) imaging to diffusion tensor imaging (DTI), dynamic susceptibility contrast (DSC) imaging, and dynamic contrast-enhanced (DCE) imaging in differentiating recurrent diffuse gliomas (World Health Organization grade II-IV) from treatment-induced change after concurrent chemoradiotherapy or radiotherapy. This study included 36 patients (25 patients with recurrent gliomas and 11 with treatment-induced changes) with post-treatment gliomas. The mean values of apparent diffusion coefficient (ADC), fractional anisotropy (FA), normalized cerebral blood volume (nCBV), normalized cerebral blood flow, volume transfer constant, rate transfer coefficient, extravascular extracellular volume fraction, plasma volume fraction, and APT asymmetry index were assessed. Independent quantitative parameters were investigated to predict recurrent glioma using multivariable logistic regression. The incremental value of APT signal to other parameters was assessed by the increase of the area under the curve, net reclassification index, and integrated discrimination improvement. Univariable analysis showed that lower ADC (p = 0.018), higher FA (p = 0.031), higher nCBV (p = 0.021), and higher APT signal (p = 0.009) were associated with recurrent gliomas. In multivariable logistic regression, the diagnostic performance of the model with ADC, FA, and nCBV significantly increased when APT signal was added, with areas under the curve of 0.87 and 0.92, respectively (net reclassification index of 0.77 and integrated discrimination improvement of 0.13). APT imaging may be a useful imaging biomarker that adds value to DTI, DCE, and DSC parameters for distinguishing between recurrent gliomas and treatment-induced changes.

Diagnostic value of 3D dynamic contrast-enhanced magnetic resonance imaging in lymph node metastases of head and neck tumors: a correlation study with histology.

BackgroundAccurate staging of cervical lymph nodes (LN) is pivotal for further clinical management of patients with head and neck cancer. Functional magnetic resonance imaging (MRI) such as three-dimensional (3D) dynamic contrast-enhanced (DCE) acquisition might improve the diagnosis of cervical LN metastases.PurposeTo evaluate the additional diagnostic value of high-resolution 3D T1-weighted DCE in detecting LN metastasis compared to standard morphological imaging criteria in patients with head and neck tumors as correlated to histopathology.Material and MethodsStandard MRI with 3D DCE acquisition at voxel sizes of 1 × 1×1 mm was performed in 15 patients before surgery; 92 LN of the head and neck were histopathologically analyzed. A logistic regression analysis of semi-quantitative DCE parameters, time-intensity curve (TIC) shapes, and morphological criteria was performed to differentiate benign from malignant LN.ResultsStandard MRI was sufficient for diagnosis of malignancy in LN with a short-axis diameter ≥ 15 mm (n = 17). For LN metastases with a short-axis diameter <15 mm (n = 12), however, the combination of 3D DCE MRI parameters, TIC shapes, and LN diameter significantly increased the sensitivity and specificity of diagnosing metastases (DCE + TIC shape + LN diameter: 92% and 88% vs. DCE only: 83% and 68% (P < 0.01) vs. LN diameter only: 83% and 77% (P = 0.04).ConclusionMRI including isotropic high-resolution 3D DCE acquisition combined with morphological criteria allows an accurate assessment of small cervical LN metastases in patients with head and neck cancer. For LN ≥ 15 mm diameter, morphologic imaging may suffice to diagnose metastatic disease to the LN.