Exploring the Neural Mechanisms of Mirrored-Self Misidentification in Alzheimer's Disease.

OBJECTIVE: Alzheimer's disease (AD) is a complex neurodegenerative condition that causes a range of cognitive disturbances, including mirror-self misidentification syndrome (MSM), in which patients cannot recognize themselves in a mirror. However, the mechanism of action of MSM is not precisely known. This study aimed to explore the possible neural mechanisms of action of MSM in AD using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: This study included 48 AD patients, 13 in the MSM group and 35 in the non-MSM group. The permeability of the blood-brain barrier (BBB) was quantitatively monitored by measuring the transfer rate (Ktrans) of the contrast agent from the vasculature to the surrounding tissue using DCE-MRI. The concentration of contrast agents in different brain regions was measured, and the Patlak model was used to calculate Ktrans. Ktrans values were compared between the left and right cerebral hemispheres in different brain areas between the MSM and non-MSM groups. Additionally, the difference in Ktrans values between mild and severe MSM was assessed. Logistic regression analysis was used to examine the risk factors for MSM. RESULTS: The Mann‒Whitney U test was used to compare two groups and revealed elevated Ktrans values in the left thalamus, left putamen, left globus pallidus, left corona radiata, and right caudate in the MSM group (p < 0.05). Logistic regression analysis revealed that increased Ktrans values in the left putamen (OR = 1.53, 95% CI = 1.04, 2.26) and left globus pallidus (OR = 1.54, 95% CI = 1.02, 2.31) may be risk factors for MSM. After dividing MSM patients into mild and moderate-severe groups, the Ktrans values of the thalamus in the moderate-severe group were greater than those in the mild group (p < 0.05). CONCLUSION: Our study revealed the relationship between BBB permeability and MSM in AD. MSM is associated with BBB breakdown in the left putamen and globus pallidus. The left putamen and globus pallidus may function in mirror self-recognition. Higher BBB permeability in the thalamus may reflect the severity of AD in MSM.

A Detailed Clinical Case of Localized Prostate Tumors Treated with Nanoparticle-Assisted Sub-Ablative Laser Ablation.

AuroLase® Therapy-a nanoparticle-enabled focal therapy-has the potential to safely and effectively treat localized prostate cancer (PCa), preserving baseline functionality. This article presents a detailed case of localized PCa treated with AuroLase, providing insight on expectations from the diagnosis of PCa to one year post-treatment. AuroLase Therapy is a two-day treatment consisting of a systemic infusion of gold nanoshells (~150-nm hydrodynamic diameter) on Day 1, and sub-ablative laser treatment on Day 2. Multiparametric MRI (mpMRI) was used for tumor visualization, treatment planning, and therapy response assessment. The PCa was targeted with a MR/Ultrasound-fusion (MR/US) transperineal approach. Successful treatment was confirmed at 6 and 12 months post-treatment by the absence of disease in MR/US targeted biopsies. On the mpMRI, confined void space was evident, an indication of necrotic tissues encompassing the treated lesion, which was completely resolved at 12 months, forming a band-like scar with no evidence of recurrent tumor. The patient's urinary and sexual functions were unchanged. During the one-year follow-up, changes on the DCE sequence and in the Ktrans and ADC values assist in qualitatively and quantitatively evaluating tissue changes. The results highlight the potential of gold-nanoparticle-enabled sub-ablative laser treatment to target and control localized PCa, maintain quality of life, and preserve baseline functionality.

Correlation of Ktrans derived from dynamic contrast-enhanced MRI with treatment response and survival in locally advanced NSCLC patients undergoing induction immunochemotherapy and concurrent chemoradiotherapy.

PURPOSE: This study aimed to investigate the prognostic significance of pretreatment dynamic contrast-enhanced (DCE)-MRI parameters concerning tumor response following induction immunochemotherapy and survival outcomes in patients with locally advanced non-small cell lung cancer (NSCLC) who underwent immunotherapy-based multimodal treatments. MATERIAL AND METHODS: Unresectable stage III NSCLC patients treated by induction immunochemotherapy, concurrent chemoradiotherapy (CCRT) with or without consolidative immunotherapy from two prospective clinical trials were screened. Using the two-compartment Extend Tofts model, the parameters including Ktrans, Kep, Ve, and Vp were calculated from DCE-MRI data. The apparent diffusion coefficient was calculated from diffusion-weighted-MRI data. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to assess the predictive performance of MRI parameters. The Cox regression model was used for univariate and multivariate analysis. RESULTS: 111 unresectable stage III NSCLC patients were enrolled. Patients received two cycles of induction immunochemotherapy and CCRT, with or without consolidative immunotherapy. With the median follow-up of 22.3 months, the median progression-free survival (PFS) and overall survival (OS) were 16.3 and 23.8 months. The multivariate analysis suggested that Eastern Cooperative Oncology Group score, TNM stage and the response to induction immunochemotherapy were significantly related to both PFS and OS. After induction immunochemotherapy, 67 patients (59.8%) achieved complete response or partial response and 44 patients (40.2%) had stable disease or progressive disease. The Ktrans of primary lung tumor before induction immunochemotherapy yielded the best performance in predicting the treatment response, with an AUC of 0.800. Patients were categorized into two groups: high-Ktrans group (n=67, Ktrans＞164.3×10-3/min) and low-Ktrans group (n=44, Ktrans≤164.3×10-3/min) based on the ROC analysis. The high-Ktrans group had a significantly higher objective response rate than the low-Ktrans group (85.1% (57/67) vs 22.7% (10/44), p<0.001). The high-Ktrans group also presented better PFS (median: 21.1 vs 11.3 months, p=0.002) and OS (median: 34.3 vs 15.6 months, p=0.035) than the low-Ktrans group. CONCLUSIONS: Pretreatment Ktrans value emerged as a significant predictor of the early response to induction immunochemotherapy and survival outcomes in unresectable stage III NSCLC patients who underwent immunotherapy-based multimodal treatments. Elevated Ktrans values correlated positively with enhanced treatment response, leading to extended PFS and OS durations.

Longitudinal Evaluation of DCE-MRI as an Early Indicator of Progression after Standard Therapy in Glioblastoma.

Background and Purpose: Distinguishing treatment-induced imaging changes from progressive disease has important implications for avoiding inappropriate discontinuation of a treatment. Our goal in this study is to evaluate the utility of dynamic contrast-enhanced (DCE) perfusion MRI as a biomarker for the early detection of progression. We hypothesize that DCE-MRI may have the potential as an early predictor for the progression of disease in GBM patients when compared to the current standard of conventional MRI. Methods: We identified 26 patients from 2011 to 2023 with newly diagnosed primary glioblastoma by histopathology and gross or subtotal resection of the tumor. Then, we classified them into two groups: patients with progression of disease (POD) confirmed by pathology or change in chemotherapy and patients with stable disease without evidence of progression or need for therapy change. Finally, at least three DCE-MRI scans were performed prior to POD for the progression cohort, and three consecutive DCE-MRI scans were performed for those with stable disease. The volume of interest (VOI) was delineated by a neuroradiologist to measure the maximum values for Ktrans and plasma volume (Vp). A Friedman test was conducted to evaluate the statistical significance of the parameter changes between scans. Results: The mean interval between subsequent scans was 57.94 days, with POD-1 representing the first scan prior to POD and POD-3 representing the third scan. The normalized maximum Vp values for POD-3, POD-2, and POD-1 are 1.40, 1.86, and 3.24, respectively (FS = 18.00, p = 0.0001). It demonstrates that Vp max values are progressively increasing in the three scans prior to POD when measured by routine MRI scans. The normalized maximum Ktrans values for POD-1, POD-2, and POD-3 are 0.51, 0.09, and 0.51, respectively (FS = 1.13, p < 0.57). Conclusions: Our analysis of the longitudinal scans leading up to POD significantly correlated with increasing plasma volume (Vp). A longitudinal study for tumor perfusion change demonstrated that DCE perfusion could be utilized as an early predictor of tumor progression.

Diagnosis and monitoring denosumab therapy of giant cell tumors of bone: radiologic-pathologic correlation.

OBJECTIVE: To determine the value of CT and dynamic contrast-enhanced (DCE-)MRI for monitoring denosumab therapy of giant cell tumors of bone (GCTB) by correlating it to histopathology. MATERIALS AND METHODS: Patients with GCTB under denosumab treatment and monitored with CT and (DCE-)MRI (2012-2021) were retrospectively included. Imaging and (semi-)quantitative measurements were used to assess response/relapse. Tissue samples were analyzed using computerized segmentation for vascularization and number of neoplastic and giant cells. Pearson's correlation/Spearman's rank coefficient and Kruskal-Wallis tests were used to assess correlations between histopathology and radiology. RESULTS: Six patients (28 ± 8years; five men) were evaluated. On CT, good responders showed progressive re-ossification (+7.8HU/month) and cortical remodeling (woven bone). MRI showed an SI decrease relative to muscle on T1-weighted (-0.01 A.U./month) and on fat-saturated T2-weighted sequences (-0.03 A.U./month). Time-intensity-curves evolved from a type IV with high first pass, high amplitude, and steep wash-out to a slow type II. An increase in time-to-peak (+100%) and a decrease in Ktrans (-71%) were observed. This is consistent with microscopic examination, showing a decrease of giant cells (-76%), neoplastic cells (-63%), and blood vessels (-28%). There was a strong statistical significant inverse correlation between time-to-peak and microvessel density (ρ = -0.9, p = 0.01). Significantly less neoplastic (p = 0.03) and giant cells (p = 0.04) were found with a time-intensity curve type II, compared to a type IV. Two patients showed relapse after initial good response when stopping denosumab. Inverse imaging and pathological findings were observed. CONCLUSION: CT and (DCE-)MRI show a good correlation with pathology and allow adequate evaluation of response to denosumab and detection of therapy failure.

Higher Blood-brain barrier permeability in patients with major depressive disorder identified by DCE-MRI imaging.

BACKGROUND: Studies from animal models and clinical trials of blood and cerebrospinal fluid have proposed that blood-brain barrier (BBB) dysfunction in depression (MDD). But there are no In vivo proves focused on BBB dysfunction in MDD patients. The present study aimed to identify whether there was abnormal BBB permeability, as well as the association with clinical status in MDD patients using dynamic contrast-enhanced magnetic resonance (DCE-MRI) imaging. METHODS: Patients with MDD and healthy adults were recruited and underwent DCE-MRI and structural MRI scans. The mean volume transfer constant (Ktrans) values were calculated for a quantitative assessment of BBB leakage. For each subject, the mean Ktrans values were calculated for the whole gray matter, white matter, and 90 brain regions of the anatomical automatic labeling template (AAL). The differences in Ktrans values between patients and controls and between treated and untreated patients were compared. RESULTS: 23 MDD patients (12 males and 11 females, mean age 28.09 years) and 18 healthy controls (HC, 8 males and 10 females, mean age 30.67 years) were recruited in the study. We found that the Ktrans values in the olfactory, caudate, and thalamus were higher in MDD patients compared to healthy controls (p<0.05). The Ktrans values in the orbital lobe, anterior cingulate gyrus, putamen, and thalamus in treated patients were lower than the patients never treated. There were positive correlations between HAMD total score with Ktrans values in whole brain WM, hippocampus and thalamus. The total HAMA score was positively correlated with the Ktrans of hippocampus. CONCLUSION: These findings supported a link between blood-brain barrier leakage and depression and symptom severity. The results also suggested a role for non-invasive DCE-MRI in detecting blood-brain barrier dysfunction in depression patients.

Immune cell identity behind the Ktrans mapping of mouse glioblastoma.

Dynamic contrast-enhanced MR imaging (DCE-MRI) can assess the integrity of the blood brain barrier (BBB) and has been used in GBM patients to determine glioma grade, predict prognosis, evaluate treatment response, and differentiate treatment-induced effect from recurrence. The volume transfer constant Ktrans is the most frequently used metric in tumor assessment. Based on previous studies that a higher WHO grade of brain tumor was associated with greater impairments of immunity and that Ktrans value was associated with the pathological grading, the relationship between differential composition of immune cells in GBM tissue and dynamic changes in Ktrans mapping was anticipated in this study. The present study utilized an orthotopic allograft model of GBM in which mouse GL26 cells are implanted into Ccr2RFP/wtCx3cr1GFP/wt mice on a C57 background. The brain tumors exhibited heterogenous Ktrans values with the coefficients of variation (CV) above 75%, or relatively homogeneous Ktrans maps with CV values below 50%. The Ktrans values of homogeneous tumors ranged between 0.02/min-0.32/min with a median value of 0.10/min. The immune cell composition defined by quantitative immunohistochemistry and cell sorting was compared between the tumors with Ktrans values above 0.10/min (higher Ktrans) or below 0.10/min (lower Ktrans). Histological analysis showed that tumors with higher Ktrans values exhibited greater numbers of CCR2pos cells (257.60 ± 16.42/mm2 vs 203.23 ± 12.20/mm2, p = 0.04) and an increased ratio of CCR2pos cells to CX3CR1pos cells (1.20 ± 0.02 vs 0.38 ± 0.04, p = 0.001), the numbers of CX3CR1pos cells did not differ significantly based on Ktrans values (219.70 ± 16.20/mm2 vs 250.38 ± 21.20/mm2, p = 0.19). Flowcytometry analysis showed that tumors with higher Ktrans values (above 0.1/min) were associated with greater numbers of both overall monocytes (54.93 ± 6.81% vs 29.75 ± 3.54%, p = 0.01) and inflammatory monocytes (72.38 ± 1.49% vs 59.52 ± 2.44%, p = 0.001). In contrast, tumors with lower Ktrans values (below 0.1/min) exhibited greater numbers of patrolling monocytes (75.65 ± 4.14% vs 63 ± 6.94%, p = 0.05). In the tumors with lower Ktrans values, all three types of tumor associated cells, including patrolling monocytes, inflammatory monocytes, and microglia cells possessed a higher proportion of cells at pro-inflammatory status (41.77 ± 6.13% vs 25.06 ± 6.72%, p = 0.05; 27.50 ± 2.11% vs 20.62 ± 1.87%, p = 0.03; and 55.80 ± 9.88% vs 31.12 ± 7.31%, p = 0.05), inflammatory monocytes showed fewer anti-inflammatory cells (1.25 ± 0.62% vs 3.16 ± 3.56%, p = 0.04). Taken together, differences in Ktrans values were associated with differential immune cell phenotypes and polarizations. Ktrans mapping may therefore represent a novel approach for defining the immune status of GBM.

Ktrans Calculation Using Reference Method Corrected Native T10 for Breast Cancer Diagnosis.

Purpose: The objective of the study is to use multiple tube phantoms to generate correction factor at different spatial locations for each breast coil cuff to correct the native T10 value in the corresponding spatial location of the breast lesion. The corrected T10 value was used to compute Ktrans and analyze its diagnostic accuracy in the classification of target condition, i.e., breast tumors into malignant and benign. Materials and Methods: Both in vitro phantom study (external reference) and patient's studies were acquired on simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) Biograph molecular magnetic resonance (mMR) system using 4 channel mMR breast coil. The spatial correction factors derived using multiple tube phantom were used for a retrospective analysis of dynamic contrast-enhanced (DCE) MRI data of 39 patients with a mean age of 50 years (31-77 years) having 51 enhancing breast lesions. Results: Corrected and non-corrected receiver operating characteristic (ROC) curve analysis revealed a mean Ktrans value of 0.64 min-1 and 0.60 min-1, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy for non-corrected data were 86.21%, 81.82%, 86.20%, 81.81%, and 84.31%, respectively, and for corrected data were 93.10%, 86.36%, 90%, 90.47%, and 90.20% respectively. The area under curve (AUC) of corrected data was improved to 0.959 (95% confidence interval [CI] 0.862-0.994) from 0.824 (95% CI 0.694-0.918) of non-corrected data, and for NPV, it was improved to 90.47% from 81.81%, respectively. Conclusion: T10 values were normalized using multiple tube phantom which was used for computation of Ktrans. We found significant improvement in the diagnostic accuracy of corrected Ktrans values that results in better characterization of breast lesions.

Persistent Peri-Ablation Blood-Brain Barrier Opening After Laser Interstitial Thermal Therapy for Brain Tumors.

Purpose Laser interstitial thermal therapy (LITT) is a minimally invasive, image-guided, cytoreductive procedure to treat recurrent glioblastoma. This study implemented dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) methods and employed a model selection paradigm to localize and quantify post-LITT blood-brain barrier (BBB) permeability in the ablation vicinity. Serum levels of neuron-specific enolase (NSE), a peripheral marker of increased BBB permeability, were measured. Methods Seventeen patients were enrolled in the study. Using an enzyme-linked immunosorbent assay, serum NSE was measured preoperatively, 24 hours postoperatively, and at two, eight, 12, and 16 weeks postoperatively, depending on postoperative adjuvant treatment. Of the 17 patients, four had longitudinal DCE-MRI data available, from which blood-to-brain forward volumetric transfer constant (Ktrans) data were assessed. Imaging was performed preoperatively, 24 hours postoperatively, and between two and eight weeks postoperatively. Results Serum NSE increased at 24 hours following ablation (p=0.04), peaked at two weeks, and returned to baseline by eight weeks postoperatively. Ktrans was found to be elevated in the peri-ablation periphery 24 hours after the procedure. This increase persisted for two weeks. Conclusion Following the LITT procedure, serum NSE levels and peri-ablation Ktrans estimated from DCE-MRI demonstrated increases during the first two weeks after ablation, suggesting transiently increased BBB permeability.

Comparison of DCE-MRI parametric mapping using MP2RAGE and variable flip angle T1 mapping.

Quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) measures the rate of transfer of contrast agent from the vascular space to the tissue space by fitting signal-time data to pharmacokinetic models. However, these models are very sensitive to errors in T1 mapping. Accurate T1 mapping is necessary for high quality quantitative DCE-MRI studies. This study compares magnetization prepared rapid (two) gradient echo sequence (MP2RAGE) T1-mapping accuracy to the conventional variable flip angle (VFA) approach, and also determines the effect of the new T1-mapping method on the Ktrans parameter. VFA and MP2RAGE T1 values were compared to the gold standard inverse recovery (IR) method in phantom over manually drawn ROIs. In vivo, ROIs were manually drawn over prostate and prostatic lesions. Average T1 values over ROIs were compared and Ktrans maps for each method were calculated via the extended Tofts model. VFA-T1 maps overestimated T1 values by up to 50% compared to gold standard IR T1 values in phantom. MP2RAGE differed by up to 9%. MP2RAGE-T1 and Ktrans values were significantly different from VFA values over prostatic lesions (p < 0.05). Ktrans was consistently underestimated using VFA compared to MP2RAGE (p < 0.05). MP2RAGE T1 maps are shown to be more accurate, leading to more reliable pharmacokinetic modeling. This can potentially lead to better lesion characterization and improve clinical outcomes.

Quantitative DCE-MRI prediction of breast cancer recurrence following neoadjuvant chemotherapy: a preliminary study.

INTRODUCTION: Breast cancer patients treated with neoadjuvant chemotherapy (NACT) are at risk of recurrence depending on clinicopathological characteristics. This preliminary study aimed to investigate the predictive performances of quantitative dynamic contrast-enhanced (DCE) MRI parameters, alone and in combination with clinicopathological variables, for prediction of recurrence in patients treated with NACT. METHODS: Forty-seven patients underwent pre- and post-NACT MRI exams including high spatiotemporal resolution DCE-MRI. The Shutter-Speed model was employed to perform pharmacokinetic analysis of the DCE-MRI data and estimate the Ktrans, ve, kep, and τi parameters. Univariable logistic regression was used to assess predictive accuracy for recurrence for each MRI metric, while Firth logistic regression was used to evaluate predictive performances for models with multi-clinicopathological variables and in combination with a single MRI metric or the first principal components of all MRI metrics. RESULTS: Pre- and post-NACT DCE-MRI parameters performed better than tumor size measurement in prediction of recurrence, whether alone or in combination with clinicopathological variables. Combining post-NACT Ktrans with residual cancer burden and age showed the best improvement in predictive performance with ROC AUC = 0.965. CONCLUSION: Accurate prediction of recurrence pre- and/or post-NACT through integration of imaging markers and clinicopathological variables may help improve clinical decision making in adjusting NACT and/or adjuvant treatment regimens to reduce the risk of recurrence and improve survival outcome.

Efficacy evaluation of contrast-enhanced magnetic resonance imaging in differentiating glioma from metastatic tumor of the brain and exploration of its association with patients' neurological function.

Objective: To determine the efficacy of contrast-enhanced MRI in differentiating glioma (GL) from the metastatic tumor of the brain (MTB) and its association with patients' neurological function. Methods: A retrospective analysis was conducted on 49 cases of pathologically confirmed GL and 42 cases of MTB admitted between April 2019 and January 2022. All patients were examined by a set of MRI sequences that included T1WI, T2WI, FLAIR, and DWI. The values of fractional anisotropy (FA), apparent diffusion coefficient (ADC), and operation coefficient (Ktrans) were calculated by taking the tumor parenchyma area, cystic area, and peritumor edema area as the regions of interest (ROIs). And according to the Mini-mental state examination (MMSE) results, the contrast-enhanced MRI with patients' neurological dysfunction was observed. Results: The clinical symptoms and MRI findings of MTB and GL were basically the same, mainly showing neurological symptoms. The tumor parenchyma area and cystic area were mainly located in the tumor periphery and tumor central area, respectively, while the peritumor edema area was widely distributed, showing an irregular patchy edema zone. Contrast-enhanced scans suggested an obvious enhancement in the tumor parenchymal area, presenting with nodular and annular enhancement, but no enhancement in the tumor cystic and peritumor edema areas. There was no difference between GL and MTB in FA values of tumor cystic area and peritumor edema area (P > 0.05), but the FA value of the parenchyma area of GL was higher (P < 0.05). Besides, GL and MTB showed no difference in ADC and Ktrans values (P > 0.05), while the former presented lower ADC values and higher Ktrans values of the peritumor edema area than the latter (P < 0.05). In patients with GL and MTB, the FA and Ktrans values of all ROIs in those with neurological dysfunction were higher compared with those without neurological dysfunction, while the ADC values were lower (P < 0.05). Conclusion: Contrast-enhanced MRI of peritumor edema area can effectively distinguish GL from MTB, and improve the accuracy of early clinical screening, thus providing more reliable life security for patients.

Early stage T1-weighted perfusion magnetic resonance imaging: a factor that predicts local control response in patients with meningioma who underwent gamma-knife radiosurgery.

BACKGROUND: Gamma-knife radiosurgery (GKRS) is an alternative treatment option for selected intracranial meningiomas. The study's aim is to demonstrate the advantages of T1-weighted perfusion magnetic resonance imaging (T1-PMRI) by measuring the volume transfer coefficient (Ktrans) values in the prediction of local response for patients with meningioma who have undergone GKRS consecutively. METHODS: The data of patients diagnosed radiologically with WHO grade 1 intracranial meningiomas was collected prospectively. The patients who were treated consecutively with GKRS at our institution (September 2017-September 2018) were included. After GKRS, the patients were followed up at the defined periods with routine contrast-enhanced MRI and T1-PMRI by measuring the Ktrans. The comparison between the pre-treatment and third-month post-treatment (PO3M) Ktrans was done using the Wilcoxon signed-rank test. RESULTS: Thirty-one patients with 36 tumors have undergone GKRS. Twenty-two patients were female. The mean age was 55.3 years. The mean pre-GKRS volume was 7.67 ccs. The mean 50% radiation isodose was 12.2 Gy. The local tumor control rate was 100%. Fourteen tumors were regressed fully at the last MRI. PO3M Ktrans decreased when compared with the pre-GKRS values (p < 0.0001). However, the numerical decrease in tumor volumes on contrast-enhanced MRI was not statistically significant (p = 0.117). CONCLUSION: Changes between Ktrans on PO3M and pre-GKRS T1-PMRI were more useful in determining the early response to GKRS in patients with meningioma than volumetric changes. Therefore, Ktrans should be taken as a reference to predict the early response to GKRS in follow-up imaging scans.

Dynamic Contrast-Enhanced MR Perfusion in Differentiation of Benign and Malignant Brain Lesions.

BACKGROUND: We aimed to differentiate Glioblastoma Multiforme (GBM) from benign lesions like Developmental Venous Anomaly (DVA) and Cavernous Malformation (CM) by Dynamic Contrast-Enhanced MR Perfusion (DCE-MRP) markers such as Ktrans, Ve, Kep, and IAUC. METHODS: We retrospectively evaluated 20 patients; 10 GBM as the malignant group, 5 CM and 5 DVA as the benign group. Ktrans, Kep, Ve, and IAUC parameters were measured by DCE-MRP, within the lesion, at perilesional nonenhancing white matter (PLWM) and contralateral normal appearing white matter (CLWM). RESULTS: All benign and malignant lesions exhibited significantly increased Ktrans, Ve, and IAUC values compared to PLWM and CLWM (p < 0.001, p=0.006 and p<0.001). Subtracted Kep values between lesion and PLWM were significantly different between the benign and malignant groups, as the malignant group exhibited higher subtracted Kep values (p 0.035). For the malignant group; Ktrans and IAUC values at the lesion were positively correlated (r 0.911), while Kep and Ve at CLWM were negatively and strongly correlated (r 0.798). For the benign group; Ktrans with Ve and Ktrans with IAUC at lesion (r 0.708 and r 0.816 respectively), Ktrans and IAUC at PLWM (r 0.809), Ktrans and IAUC at CLWM(r 0.798) were strongly and positively correlated. Ktrans, Ve, and IAUC values can be used to restrict the lesion in both groups. CONCLUSION: Ktrans strongly correlates with IAUC and they can be used instead of each other in both benign and malignant lesions. Classical DCE-MRP parameters cannot be used in the differentiation of malignant lesions from benign vascular lesions. However, subtracted Kep values can be used to differentiate GBM from benign vascular lesions.

The Assessment of Prostate Cancer Aggressiveness Using a Combination of Quantitative Diffusion-Weighted Imaging and Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

OBJECTIVE: To explore the value of combining dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) quantitative parameters with apparent diffusion coefficient (ADC) values in the diagnosis of prostate cancer. METHODS: The clinical data of 146 patients with prostate lesions, including 87 patients with prostate cancer (PCa) and 59 with benign prostatic hyperplasia (BPH), were collected. After DCE-MRI and diffusion-weighted imaging (DWI) prostate scans, the magnitude of the DCE-MRI transfer constant (Ktrans ), rate constant (kep ), the volume of the extravascular extracellular space (ve ), and the ADC between the groups were compared, and the correlations between the DCE-MRI parameters and Gleason scores were analyzed. The diagnostic efficacy of these quantitative parameters was assessed by the area under the receiver operating characteristic (ROC) curve. RESULTS: The DCE-MRI parameters Ktrans and kep were significantly greater in the PCa group than in the BPH group (p < 0.05). The ROC curve showed the area under the Ktrans, kep , and ADC curves to be 0.665, 0.658, and 0.782, respectively. When all three quantitative indicators were combined, the area under the ROC curve was 0.904, with sensitivity and specificity rates of 83.6% and 93.7%, respectively. The Gleason scores were positively correlated with the Ktrans, kep , and ve (r = 0.39, 0.572, 0.30, respectively; p < 0.05) and negatively correlated with the ADC (r = -0.525; p < 0.05). CONCLUSION: The DCE-MRI quantitative parameters Ktrans and kep , as well as the ADC value, provided effective references for the differential diagnosis of PCa and BPH, as well as more precise and reliable quantitative parameters for grading the aggressiveness of PCa.

Blood-brain barrier dysfunction significantly correlates with serum matrix metalloproteinase-7 (MMP-7) following traumatic brain injury.

OBJECTIVES: To determine if radiological evidence of blood brain barrier (BBB) dysfunction, measured using Dynamic Contrast Enhanced MRI (DCE-MRI), correlates with serum matrix metalloproteinase (MMP) levels in traumatic brain injury (TBI) patients, and thereby, identify a potential biomarker for BBB dysfunction. PATIENTS AND METHODS: 20 patients with a mild, moderate, or severe TBI underwent a DCE-MRI scan and BBB dysfunction was interpreted from KTrans. KTrans is a measure of capillary permeability that reflects the efflux of gadolinium contrast into the extra-cellar space. The serum samples were concurrently collected and later analysed for MMP-1, -2, -7, -9, and -10 levels using an ELISA assay. Statistical correlations between MMP levels and the KTrans value were calculated. Multiple testing was corrected using the Benjamin-Hochberg method to control the false-discovery rate (FDR). RESULTS: Serum MMP-1 values ranged from 1.5 to 49.6 ng/ml (12 ± 12.7), MMP-2 values from 58.3 to 174.1 ng/ml (109.5 ± 26.7), MMP-7 from 1.5 to 31.5 ng/mL (10 ± 7.4), MMP-9 from 128.6 to 1917.5 ng/ml (647.7 ± 749.6) and MMP-10 from 0.1 to 0.6 ng/mL (0.3 ± 0.2). Non-parametric Spearman correlation analysis on the data showed significant positive relationship between KTrans and MMP-7 (r = 0.55, p < 0.01). Correlations were also found between KTrans and MMP-1 (r = 0.74, p < 0.0002) and MMP-2 (r = 0.5, p < 0.025) but the actual MMP values were not above reference ranges, limiting the interpretation of results. Statistically significant correlations between KTrans and either MMP-9 or -10 were not found. CONCLUSION: This is the first study to show a correlation between DCE measures and MMP values in patients with a TBI. Our results support the suggestion that serum MMP-7 may be considered as a peripheral biomarker quantifying BBB dysfunction in TBI patients.

Imaging acute effects of bevacizumab on tumor vascular kinetics in a preclinical orthotopic model of U251 glioma.

The effect of a human vascular endothelial growth factor antibody on the vasculature of human tumor grown in rat brain was studied. Using dynamic contrast-enhanced magnetic resonance imaging, the effects of intravenous bevacizumab (Avastin; 10 mg/kg) were examined before and at postadministration times of 1, 2, 4, 8, 12 and 24 h (N = 26; 4-5 per time point) in a rat model of orthotopic, U251 glioblastoma (GBM). The commonly estimated vascular parameters for an MR contrast agent were: (i) plasma distribution volume (vp ), (ii) forward volumetric transfer constant (Ktrans ) and (iii) reverse transfer constant (kep ). In addition, extracellular distribution volume (VD ) was estimated in the tumor (VD-tumor ), tumor edge (VD-edge ) and the mostly normal tumor periphery (VD-peri ), along with tumor blood flow (TBF), peri-tumoral hydraulic conductivity (K) and interstitial flow (Flux) and tumor interstitial fluid pressure (TIFP). Studied as % changes from baseline, the 2-h post-treatment time point began showing significant decreases in vp , VD-tumor, VD-edge and VD-peri , as well as K, with these changes persisting at 4 and 8 h in vp , K, VD-tumor, -edge and -peri (t-tests; p < 0.05-0.01). Decreases in Ktrans were observed at the 2- and 4-h time points (p < 0.05), while interstitial volume fraction (ve ; = Ktrans /kep ) showed a significant decrease only at the 2-h time point (p < 0.05). Sustained decreases in Flux were observed from 2 to 24 h (p < 0.01) while TBF and TIFP showed delayed responses, increases in the former at 12 and 24 h and a decrease in the latter only at 12 h. These imaging biomarkers of tumor vascular kinetics describe the short-term temporal changes in physical spaces and fluid flows in a model of GBM after Avastin administration.

Multiparametric Magnetic Resonance Imaging, 68Ga Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography, and Respective Quantitative Parameters in Detection and Localization of Clinically Significant Prostate Cancer in Intermediate- and High-Risk Group Patients: An Indian Demographic Study.

OBJECTIVES: The objective of this study was to evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) and 68Ga prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET-CT) and respective quantitative parameters (Ktrans - influx rate contrast, Kep - efflux rate constant, ADC - apparent diffusion coefficient, and SUVmax ratio - prostate SUVmax to background SUVmax ratio) in detection and localization of clinically significant prostate cancer (CSPCa) in D'Amico intermediate- and high-risk group patients (prostate-specific antigen [PSA] >10 ng/ml). METHODOLOGY: The study included thirty-three consecutive adult men with serum prostate specific antigen >10ng/ml, and systematic 12 core prostate biopsy proven prostate cancer. All the 33 patients, were evaluated with mpMRI, and 68Ga PSMA PET-CT. The biopsy specimens and imaging were evaluated for 12 sectors per prostate by a predetermined scheme. RESULTS: MpMRI Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score ≥3 showed higher sensitivity than 68Ga PSMA PET-CT (96.3% vs. 82.4%), with similar specificity (54.5% vs. 54.5%) (n = 33 patients, 396 sectors). Combined use of MRI and 68Ga PSMA PET-CT in parallel increased sensitivity (99.5%) and NPV (98.7%) for detection of CSPCa and combined use of MRI and 68Ga PSMA PET-CT in series increased specificity (71.8%) and PPV (71.5%) (n = 33 patients, 396 sectors). ADC showed a strong negative correlation with Gleason score (r = -0.77), and the highest discriminative ability for detection and localization of CSPCa (area under curve [AUC]: 0.91), followed by Ktrans (r = 0.74; AUC: 0.89), PI-RADS (0.73; 0.86), SUVmax ratio (0.49; 0.74), and Kep (0.24; 0.66). CONCLUSION: MpMRI PI-RADS v2 score and 68Ga PSMA PET-CT (individually as well as in combination) are reliable tool for detection and localization of CSPCa. Quantitative MRI and 68Ga PSMA PET-CT parameters have potential to predict Gleason score and detect CSPCa.

Repeatability of tumor perfusion kinetics from dynamic contrast-enhanced MRI in glioblastoma.

BACKGROUND: Dynamic contrast-enhanced MRI (DCE-MRI) parameters have been shown to be biomarkers for treatment response in glioblastoma (GBM). However, variations in analysis and measurement methodology complicate determination of biological changes measured via DCE. The aim of this study is to quantify DCE-MRI variations attributable to analysis methodology and image quality in GBM patients. METHODS: The Extended Tofts model (eTM) and Leaky Tracer Kinetic Model (LTKM), with manually and automatically segmented vascular input functions (VIFs), were used to calculate perfusion kinetic parameters from 29 GBM patients with double-baseline DCE-MRI data. DCE-MRI images were acquired 2-5 days apart with no change in treatment. Repeatability of kinetic parameters was quantified with Bland-Altman and percent repeatability coefficient (%RC) analysis. RESULTS: The perfusion parameter with the least RC was the plasma volume fraction (v p ), with a %RC of 53%. The extra-cellular extra-vascular volume fraction (v e ) %RC was 82% and 81%, for extended Tofts-Kety Model (eTM) and LTKM respectively. The %RC of the volume transfer rate constant (K trans ) was 72% for the eTM, and 82% for the LTKM, respectively. Using an automatic VIF resulted in smaller %RCs for all model parameters, as compared to manual VIF. CONCLUSIONS: As much as 72% change in K trans (eTM, autoVIF) can be attributable to non-biological changes in the 2-5 days between double-baseline imaging. Poor K trans repeatability may result from inferior temporal resolution and short image acquisition time. This variation suggests DCE-MRI repeatability studies should be performed institutionally, using an automatic VIF method and following quantitative imaging biomarkers alliance guidelines.

Role of Various DW MRI and DCE MRI Parameters as Predictors of Malignancy in Solid Pulmonary Lesions.

PURPOSE: We aimed to evaluate various diffusion and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) parameters in differentiating malignant from benign pulmonary lesions. METHODS: We enrolled 31 (22 males) patients who had solid pulmonary lesion(s) >2 cm in our cross sectional study. Of these, 23 (74.2%) were found to be malignant on histopathology. Dynamic contrast-enhanced MRI was performed using 36 dynamic measurements (volumetric interpolated breath-hold examination). Diffusion-weighted MRI (DW MRI) performed at b value of 800 s/mm2. We measured different diffusion and perfusion parameters, for example, diffusion-weighted imaging (DWI) SI, mean apparent diffusion coefficient (ADC), minimum ADC, lesion-to-spinal cord ratio, DWI score, T2 score, Ktrans, Kep, and Ve. We stratified values of each parameter as high if it was >median of values observed in our data set and low if it was ≤median. Normally distributed data were compared by unpaired t test, whereas non-normal continuous data were compared by Kruskal Wallis-H test. We applied Wilson score method to calculate sensitivity, specificity, and predictive values of parameters that were statistically significant by type of lesion with reference to histopathological examination as gold standard. RESULTS: Diffusion-weighted imaging SI, mean ADC, minimum ADC, DWI score and Ktrans values were found to be significantly different (P value < .05) by type of lesion. Ktrans was found to have the highest diagnostic accuracy (74.2%) among these parameters. CONCLUSION: Ktrans and mean ADC had similar sensitivity of 65.2%. However, Ktrans had highest diagnostic accuracy among various DWI and DCE MRI parameters in predicting malignancy in solid pulmonary lesions. In our study, we found a cutoff value 0.251 min-1 for Ktrans as 100% specific.