Ktrans Values Research Articles

Dynamic Contrast-enhanced MRI Quantification of Altered Vascular Permeability in Autoimmune Encephalitis.

Background Blood-brain barrier (BBB) permeability change is a possible pathologic mechanism of autoimmune encephalitis. Purpose To evaluate the change in BBB permeability in patients with autoimmune encephalitis as compared with healthy controls by using dynamic contrast-enhanced (DCE) MRI and to explore its predictive value for treatment response in patients. Materials and Methods This single-center retrospective study included consecutive patients with probable or possible autoimmune encephalitis and healthy controls who underwent DCE MRI between April 2020 and May 2021. Automatic volumetric segmentation was performed on three-dimensional T1-weighted images, and volume transfer constant (Ktrans) values were calculated at encephalitis-associated brain regions. Ktrans values were compared between the patients and controls, with adjustment for age and sex with use of a nonparametric approach. The Wilcoxon rank sum test was performed to compare Ktrans values of the good (improvement in modified Rankin Scale [mRS] score of at least two points or achievement of an mRS score of ≤2) and poor (improvement in mRS score of less than two points and achievement of an mRS score >2) treatment response groups among the patients. Results Thirty-eight patients with autoimmune encephalitis (median age, 38 years [IQR, 29-59 years]; 20 [53%] female) and 17 controls (median age, 71 years [IQR, 63-77 years]; 12 [71%] female) were included. All brain regions showed higher Ktrans values in patients as compared with controls (P < .001). The median difference in Ktrans between the patients and controls was largest in the right parahippocampal gyrus (25.1 × 10-4 min-1 [95% CI: 17.6, 43.4]). Among patients, the poor treatment response group had higher baseline Ktrans values in both cerebellar cortices (P = .03), the left cerebellar cortex (P = .02), right cerebellar cortex (P = .045), left cerebral cortex (P = .045), and left postcentral gyrus (P = .03) than the good treatment response group. Conclusion DCE MRI demonstrated that BBB permeability was increased in all brain regions in patients with autoimmune encephalitis as compared with controls, and baseline Ktrans values were higher in patients with poor treatment response in the cerebellar cortex, left cerebral cortex, and left postcentral gyrus as compared with the good response group. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Filippi and Rocca in this issue.

Dynamic contrast-enhanced magnetic resonance imaging assessment of residual tumor angiogenesis after insufficient microwave ablation and donafenib adjuvant therapy

To analyze the correlation between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) permeability parameters and serum vascular endothelial growth factor (VEGF) levels in a rabbit VX2 liver cancer model with insufficient microwave ablation (MWA), to observe the dynamic changes in residual tumor angiogenesis in the short term after MWA, and to assess the effectiveness of donafenib as adjuvant therapy. Forty rabbits with VX2 liver tumors were randomly divided into three groups: an insufficient MWA group (n = 15), a combined treatment group (n = 15) and a control group (n = 10). The dynamic changes in VEGF expression after MWA and the effectiveness of donafenib as adjuvant therapy were evaluated by DCE-MRI and serum VEGF levels before surgery and 1, 3, 7, and 14 days after surgery. The correlation between the volume translate constant (Ktrans) of DCE-MRI parameters and serum VEGF levels fluctuated after ablation, but the coefficient was always positive (all p < 0.001). Repeated-measures ANOVA revealed significant changes in the serum VEGF concentration (F = 40.905, p < 0.001; partial η2 = 0.689), Ktrans (F = 13.388, p < 0.001; partial η2 = 0.420), and tumor diameter in each group (F = 34.065, p < 0.001; partial η2 = 0.648) at all five time points. Pairwise comparisons showed that the serum VEGF level, Ktrans value and tumor diameter in the insufficient MWA group and combined treatment group were significantly lower at 1 d than in the control group, but these values gradually increased over time (all p < 0.05). Ktrans and tumor diameter were significantly greater in the insufficient MWA group than in the control group at 14 days (all p < 0.05). The serum VEGF concentration, Ktrans, and tumor diameter were significantly lower in the combined treatment group than in the other two groups at 3, 7, and 14 days (all p < 0.05). Ktrans is positively correlated with the serum VEGF concentration. Ktrans and the serum VEGF concentration changed significantly after treatment with insufficient ablation or in combination with donafenib, and Ktrans may change faster. Insufficient MWA promotes the progression of residual tumors. Adjuvant treatment with donafenib is effective.

Values of multiparametric and biparametric MRI in diagnosing clinically significant prostate cancer: a multivariate analysis

BackgroundTo investigate the value of semi-quantitative and quantitative parameters (PI-RADS score, T2WI score, ADC, Ktrans, and Kep) based on multiparametric MRI (mpMRI) or biparametric MRI (bpMRI) combined with prostate specific antigen density (PSAD) in detecting clinically significant prostate cancer (csPCa).MethodsA total of 561 patients (276 with csPCa; 285 with non-csPCa) with biopsy-confirmed prostate diseases who underwent preoperative mpMRI were included. Prostate volume was measured for calculation of PSAD. Prostate index lesions were scored on a five-point scale on T2WI images (T2WI score) and mpMRI images (PI-RADS score) according to the PI-RADS v2.1 scoring standard. DWI and DCE-MRI images were processed to measure the quantitative parameters of the index lesion, including ADC, Kep, and Ktrans values. The predictors of csPCa were screened by logistics regression analysis. Predictive models of bpMRI and mpMRI were established. ROC curves were used to evaluate the efficacy of parameters and the model in diagnosing csPCa.ResultsThe independent diagnostic accuracy of PSA density, PI-RADS score, T2WI score, ADCrec, Ktrans, and Kep for csPCa were 80.2%, 89.5%, 88.3%, 84.6%, 58.5% and 61.6%, respectively. The diagnostic accuracy of bpMRI T2WI score and ADC value combined with PSAD was higher than that of PI-RADS score. The combination of mpMRI PI‑RADS score, ADC value with PSAD had the highest diagnostic accuracy.ConclusionsPI-RADS score according to the PI-RADS v2.1 scoring standard was the most accurate independent diagnostic index. The predictive value of bpMRI model for csPCa was slightly lower than that of mpMRI model, but higher than that of PI-RADS score.

Glioma grading using an optimized T1-weighted dynamic contrast-enhanced magnetic resonance imaging paradigm

BackgroundGlioma grading is a critical procedure for selecting the most effective treatment policy. Biopsy result is the gold standard method for glioma grading, but inherent sampling errors in the biopsy procedure could lead to tumor misclassification.AimThis study evaluated grading performances of a more comprehensive collection of the physiological indices quantified using an optimized dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) paradigm for glioma grading.MethodsThirty-five patients with glioma underwent DCE-MR imaging to evaluate the grading performances of DCE-MRI-derived physiological indices. The statistical differences in the physiological indices between the different grades of gliomas were studied, and the grading performances of these parameters were evaluated using the leave-one-out cross-validation method.ResultsThere were significant statistical differences in DCE-MRI-derived physiological indices between the different grades of gliomas. The mean rCBVs for grade II (low-grade glioma, LGG), grade III, grade IV, and high-grade (HGG) gliomas were 2.03 ± 0.78, 3.61 ± 1.64, 7.14 ± 3.19, and 5.28 ± 3.02, respectively. The mean rCBFs of 1.94 ± 0.97, 2.67 ± 0.96, 4.57 ± 1.77, and 3.57 ± 1.68 were, respectively, quantified for grade II (LGG), grade III, grade IV, and high-grade gliomas. The leave-one-out cross-validation method indicates that the grades of glioma tumors could be determined based on a specific threshold for each physiological index; for example, the optimal cutoff values for rCBF, rCBV, Ktrans, Kep, and Vp indices to distinguish between HGGs and LGGs were 2.11, 2.80, 0.025 mL/g min, 0.29 min−1, and 0.065 mL/g, respectively.ConclusionsFrom the results, it could be concluded that glioma grades could be determined using DCE-MRI-derived physiological indices with an acceptable agreement with histopathological results.

Microvascular permeability and texture analysis of bone marrow in diabetic rabbits with critical limb ischemia based on dynamic contrast-enhanced magnetic resonance imaging.

Early on in the development of diabetes, skeletal muscles can exhibit microarchitectural changes that can be detected using texture analysis (TA) based on volume transfer constant (Ktrans) maps. Nevertheless, there have been few studies and thus we evaluated microvascular permeability and the TA of the bone marrow in diabetics with critical limb ischemia (CLI). Eighteen male rabbits were randomly assigned equally into an operation group with hindlimb ischemia and diabetes, a sham-operated group with diabetes only, and a control group. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) was performed on all rabbits at predetermined intervals (1, 5, 10, 15, 20, and 25 days post-surgery). The pharmacokinetic model was used to generate the permeability parameters, while the textural parameters were derived from the Ktrans map. Data analysis methods included the independent sample t-test, Mann-Whitney U test, repeated-measures analysis of variance, and Pearson correlation tests. The Ktrans values reached a minimum on day 1 after ischemia induction, then gradually recovered, but remained lower than those of the sham-operated group. The volume fraction only showed a significant difference between the operation group and the sham-operated group on day 5 post-surgery, but not in the extravascular extracellular space volume fraction at all time points. A significantly reduced Ktrans on day 1, a decreased number of bone trabeculae (Tb.N), and the area of bone trabeculae (Tb.Ar), and an increased microvessel density on day 25 in the operation group compared with the sham-operated group were observed. At each time point, there was a discernible difference between the two groups in the mean value, mean of positive pixels, and sumAverage. The early stages of diabetic bone marrow with CLI can be evaluated by DCE-MRI for microvascular permeability. Texture analysis based on DCE-MRI could act as an imaging discriminator and new radiological analysis tool for critical limb ischemia in diabetes mellitus.

Diagnostic Utility of Integration of Dynamic Contrast-Enhanced and Dynamic Susceptibility Contrast MR Perfusion Employing Split Bolus Technique in Differentiating High-Grade Glioma.

Background : Despite documented correlation between glioma grades and dynamic contrast-enhanced (DCE) magnetic resonance (MR) perfusion-derived parameters, and its inherent advantages over dynamic susceptibility contrast (DSC) perfusion, the former remains underutilized in clinical practice. Given the inherent spatial heterogeneity in high-grade diffuse glioma (HGG) and assessment of different perfusion parameters by DCE (extravascular extracellular space volume [Ve] and volume transfer constant in unit time [k-trans]) and DSC (rCBV), integration of the two into a protocol could provide a holistic assessment. Considering therapeutic and prognostic implications of differentiating WHO grade 3 from 4, we analyzed the two grades based on a combined DCE and DSC perfusion. Methods : Perfusion sequences were performed on 3-T MR. Cumulative dose of 0.1 mmol/kg of gadodiamide, split into two equal boluses, was administered with an interval of 6 minutes between the DCE and DSC sequences. DCE data were analyzed utilizing commercially available GenIQ software. Results : Of the 41 cases of diffuse gliomas analyzed, 24 were WHO grade III and 17 grade IV gliomas (2016 WHO classification). To differentiate grade III and IV gliomas, Ve cut-off value of 0.178 provided the best combination of sensitivity (88.24%) and specificity (87.50%; AUC: 0.920; p < 0.001). A relative cerebral blood volume (rCBV) of value 3.64 yielded a sensitivity of 70.59% and specificity of 62.50% ( p = 0.018). The k-trans value, although higher in grade III than in grade IV gliomas, did not reach statistical significance ( p = 0.108). Conclusion : Uniqueness of employed combined perfusion technique, treatment naïve patients at imaging, user-friendly postprocessing software utilization, and ability of Ve and rCBV to differentiate between grade III and IV gliomas ( p < 0.05) are the strengths of the present study, contributing to the existing literature and moving a step closer to achieving accurate MR perfusion-based glioma grading.

Dynamic contrast enhanced high field magnetic resonance imaging for canine primary intracranial neoplasia.

Distinguishing meningiomas from other intracranial neoplasms is clinically relevant as the prognostic and therapeutic implications differ greatly and influence clinical decision making. Dynamic contrast-enhanced MRI (DCE-MRI) is an imaging technique that assists with characterisation of physiologic alterations such as blood flow and tissue vascular permeability. Quantitative pharmacokinetic analysis utilising DCE-MRI has not been studied in canine neuro-oncology. A retrospective study was performed in canine patients that underwent DCE-MRI with an imaging diagnosis of an intracranial meningioma and surgery for histopathological diagnosis. Kinetic parameters Ktrans and cerebral blood flow were measured and compared to assess whether differences could be identified between meningiomas and other intracranial neoplasms. Six dogs with meningiomas and 3 dogs with other intracranial neoplasms were included for statistical analysis. Cerebral blood flow values were found to be statistically higher within meningiomas compared to other intracranial neoplasms. Ktrans values were higher within meningiomas than in other types of intracranial tumours, however this difference did not reach statistical significance. Based on the results of this study cerebral blood flow measurement can be utilised to differentiate canine intracranial meningiomas from other similar appearing intracranial tumours.

Analysis of Clinical Diagnostic Value of Dynamic Contrast-Enhanced Magnetic Resonance Imaging Combined with MRI in Early Breast Cancer

A study involving 73 patients with early breast space-occupying diseases (41 malignant, 32 benign) utilized 1.5T quantitative dynamic enhanced magnetic resonance imaging to measure lesion-specific parameters. These included the contrast medium’s transfer rate from intravascular to extravascular (Ktrans), return rate to blood vessels (Kep), and tumor vessel volume fraction (Vp). Pathological results post-surgery served as the gold standard. Comparisons between benign and malignant groups, as well as malignant subtypes, were made. Malignant lesions exhibited varied Ktrans (0.108–2.810 min−1) and Vp (0.0018–0.743 ml) values. Benign lesions had Ktrans (0.125–2.472 min−1), Kep (0.008–1.760 min−1), and Vp (0.006–0.816 ml) values. Significant differences were observed in Ktrans and Vp (P &lt; 0.05), but not in Kep and Vp (P &gt; 0.05). While differences between hormonal and HER2 statuses were minimal, Kep in HER2-positive tumors was notable (P &lt; 0.05). Subtype comparisons showed no significant Ktrans variation (P &gt; 0.05) but differences in Kep and Vp. In conclusion, Ktrans is crucial for diagnosing early breast cancer and distinguishing between benign and malignant diseases. The study underscores the potential of quantitative dynamic contrast-enhanced MRI in breast cancer diagnosis

The significance of PI-RADS v2.1 score combined with quantitative parameters of DWI and DCE-MRI in differentiating between benign prostatic hyperplasia and prostate cancer

This study investigates the efficacy of the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) score combined with quantitative metrics from Diffusion Weighted Imaging (DWI) and Dynamic Contrast Enhancement Magnetic Resonance Imaging (DCE-MRI) in differentiating between benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The data of 65 patients with prostate diseases were retrospectively analyzed, and they were divided into a BPH group (n = 34) and a PCa group (n = 31). All patients underwent a multiparametric MRI (mpMRI) examination, which included conventional MRI, DWI and DCE-MRI scans. Variables analyzed included the PI-RADS v2.1 score, apparent diffusion coefficient (ADC), volume transfer constant (Ktrans), rate constant (Kep) and extravascular space volume ratio (Ve). The diagnostic performance of the PI-RADS v2.1 score, DWI, DCE-MRI and their combined metrics in differentiating BPH from PCa was assessed using Receiver Operating Characteristic (ROC) curve analysis. The results demonstrated that the PI-RADS v2.1 scores, Ktrans and Kep values of the PCa group were significantly higher than those of the BPH group (p &lt; 0.001), while the ADC value of the PCa group was significantly lower than the BPH group (p &lt; 0.001). No significant difference was observed in the Ve value between the two groups (p = 0.596). ROC analysis indicated that the area under the curve (AUC) values for the PI-RADS v2.1 score, ADC, Ktrans, Kep, Ve and their combination parameters were 0.824, 0.916, 0.903, 0.904, 0.625 and 0.990, respectively, with the combined parameters showing higher sensitivity and specificity than any single parameter. These findings suggest that the PI-RADS v2.1 score, along with DWI and DCE-MRI sequences, are valuable tools for differentiating BPH from PCa. The quantitative parameters, including ADC, Ktrans and Kep values, offer significant imaging references for clinical assessment, and the combination parameters can significantly enhance diagnostic accuracy.

Blood‐brain barrier disruption measured by dynamic contrast‐enhanced MRI in Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) is characterized by the accumulation of amyloid beta (Aβ) plaques in the brain. Blood‐brain barrier (BBB) dysfunction has been associated with AD. Aβ‐plaques have been found to disrupt the BBB, leading to increased permeability and invasion of immune cells into the CNS and triggering an inflammatory response, and contributing to neurodegeneration. In this study, we investigated BBB disruption in Alzheimer’s disease and its associations with amyloid deposition and clinical severity, and cognitive decline.MethodIn this cross‐sectional study, n = 16 AD patients were included. AD patients were defined as amyloid positive by CSF amyloid‐β42/amyloid‐β40 ratio &lt; 5,5% and a Mini‐Mental‐State Examination (MMSE) score &lt; 27. Dynamic contrast‐enhanced magnetic resonance imaging (DCE MRI), a non‐invasive imaging technique that uses intravenously injected gadolinium to quantify the permeability of the BBB has been acquired. DCE‐MRI quantification was quantified using the Patlak method. To analyse the regional degree of BBB disruption the AAL atlas was warped onto the Patlak maps and the median of each ROI was calculated. The cortical amyloid deposition has been quantified using 18F]flutemetamol β‐amyloid‐PET and cognitive performance was assessed using the Alzheimer’s Disease neuropsychological battery (CERAD‐NB). Associations were tested using linear regression models adjusted for age and sex in SPSS.ResultThe highest Ktrans values were measured in the orbitofrontal cortex (mean: 1,6×10−3 min−1). BBB dysfunction in median Ktrans values in the bilateral temporal lobe and particularly the right hippocampus were associated with decreases in the CSF amyloid‐β ratio. Furthermore, BBB dysfunction was negatively associated with cognitive decline measured by the CERAD‐NB. BBB dysfunction overlapped with amyloid PET accumulation in the parietal and temporal brain regions.ConclusionDCE MRI shows spatially localized BBB dysfunction in AD. The BBB dysfunction seems to be more severe in regions of the brain that are affected by Aβ plaques. This could support the idea that Aβ plaque contributes to BBB dysfunction in AD. BBB dysfunction also tends to be pronounced in patients with more severe cognitive impairment, suggesting that it may play a role in the progression of AD.

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

BackgroundStudies 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. MethodsPatients 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. Results23 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. ConclusionThese 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.

DDEL-04. MODULATION OF THE BLOOD-TUMOR BARRIER FOR IMPROVED DRUG DELIVERY IN GLIOBLASTOMA

Abstract Effective drug delivery remains a major challenge in glioblastoma (GBM) treatment. Specialized intercellular endothelial cell tight junctions at the blood-brain and blood-tumor barriers (BBB/BTB) represent obstacles to therapeutic efficacy by limiting intratumoral drug uptake. To understand the factors at the BTB that limit drug accessibility we performed bioinformatics analysis of TCGA data which suggested enrichment of the tight junction protein VE-cadherin (CDH5). CDH5 expression at the BTB was confirmed by immunostaining of patient GBM specimens and spatial transcriptomics using the 10X Visium platform. We found that a broadly selective protein kinase inhibitor, 6-bromoindirubin-3’-acetoxime (BIA), potently down-regulated CDH5 in cultured human cerebrovascular endothelial cells (HCMEC/D3) at the transcriptional level and this correlated with decreased trans-endothelial electrical resistance (TEER) measurement. In vivo administration of BIA (20 mg/kg IP) to mice bearing intracranial GBM xenografts showed striking downregulation of CDH5 in tumor associated endothelium. Furthermore, increased BTB permeability was shown using fluorescent tracers as well as DCE-MRI, which demonstrated elevated Ktrans values 24 hours after BIA administration. Integrated phospho-proteomic and transcriptomic analysis of BIA treated HCMEC/D3 cells support a mechanism involving p38 MAP kinase regulation of Ets-family transcription factors that drive CDH5 expression. At least a 20-fold increase in intra-tumoral accumulation of cisplatin and temozolomide was observed using G9-pCDH GBM xenografts when administered 24 h after BIA treatment. No increased drug uptake was seen in healthy brain tissue, indicating specific targeting of tumor vasculature. Efficacy studies showed extended survival when using cisplatin in combination with BIA (median 27d, p=0.0016) when compared to cisplatin (18.5d), BIA (21.5d) and control (18d). Further efficacy studies are underway. These data therefore identify the GBM-associated vasculature as a target for small molecule inhibition of tight junction formation to enhance intratumoral drug uptake. Ongoing studies are investigating the potential of this approach with a range of agents.

The value of multiparametric MRI combined with clinical prognostic parameters in predicting the 5-year survival of stage IIIC1 cervical squamous cell carcinoma

ObjectivesTo explore the value of multiparametric magnetic resonance imaging（MRI）in predicting the 5-year progression-free survival (PFS) and overall survival (OS) of cervical squamous cell carcinoma (CSCC) in 2018 FIGO stage IIIC1. MethodsThis retrospective study collected156 patients with CSCC from Dec. 2014 to Jul. 2018. Sixty-one patients underwent radical hysterectomy (RH), and 95 patients underwent concurrent chemoradiotherapy (CCRT). Clinical and MR parameters of primary tumours were analysed. A 1:1 ratio propensity score matching (PSM) was performed for the RH group and CCRT group according to T stage. The Cox proportional hazard model was used to evaluate the associations between imaging or clinical variables and PFS and OS. ResultsThe 5-year PFS and OS rates were 72.6% and 78.3%, respectively. The analysis results show that the treatment method, ADCmin < 0.604 × 10−3 mm2/s, and Ktrans < 0.699 min−1 correlated with worse PFS, while SCC-Ag > 6.7 ng/L, ADCmin < 0.604 × 10−3 mm2/s, and Ktrans < 0.699 min−1 correlated with worse OS. After PSM, we confirmed that the treatment methods did not affect the long-term survival of patients with stage IIIC1 disease, and a low Ktrans value was an independent poor prognostic factor. ConclusionFunctional MRI parameters and SCC-Ag have potential predictive value for the 5-year survival of 2018 FIGOIIIC1 CSCC. There were no significant differences in survival between CCRT and RH + adjuvant therapy for IIIC1 stage CSCC if the T stage was earlier.

Dynamic contrast-enhanced magnetic resonance imaging parameter changes as an early biomarker of tumor responses following radiation therapy in patients with spinal metastases: a systematic review.

This systematic review aims to assess and summarize the clinical values of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameter changes as early biomarkers of tumor responses following radiation therapy (RT) in patients with spinal metastases. A systematic search was conducted on five electronic databases: PubMed, Scopus, Science Direct, Cochrane, and Embase. Studies were included if they mentioned DCE-MRI parameter changes before and after RT in patients with spinal metastases with a correlation to tumor responses based on clinical and imaging criteria. The Quality Assessment of Diagnostic Accuracy Studies 2 was used to assess study quality. This systematic review included seven studies involving 107 patients. All seven studies evaluated the transfer constant (Ktrans), six studies evaluated the plasma volume fraction (Vp), three studies evaluated the extravascular extracellular space volume fraction, and two studies evaluated the rate constant. There were variations in the type of primary cancer, RT techniques used, post-treatment scan time, and median follow-up time. Despite the variations, however, the collected evidence generally suggested that significant differences could be detected in DCE-MRI parameters between before and after RT, which might reflect treatment success or failures in long-term follow-up. Responders showed higher reduction and lower values of Ktrans and Vp after RT. DCE-MRI parameters showed changes and detectable recurrences significantly earlier (up to 6 months) than conventional MRI with favorable diagnostic values. The results of this systematic review suggested that DCE-MRI parameter changes in patients with spinal metastases could be a promising tool for treatment-response assessment following RT. Lower values and higher reduction of Ktrans and Vp after treatment demonstrated good prediction of local control. Compared to conventional MRI, DCE-MRI showed more rapid changes and earlier prediction of treatment failure.

Discrimination between benign and malignant lung lesions using volumetric quantitative dynamic contrast-enhanced MRI.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is considered a promising method in lung lesion assessment. Sixty-four patients with single pulmonary lesions (SPLs) received DCE-MRI at 3.0 T. Of them, 49 cases were diagnosed with lung cancer, and 15 with benign pulmonary nodules (8 inflammatory nodules, 5 tuberculosis, and 2 abscesses). SPLs were quantitatively analyzed to determine the pulmonary lesions-related perfusion parameters, including reflux constant (Kep), volume transfer constant (Ktrans), the maximum slope of increase (MaxSlope), extravascular extracellular space volume fraction (Ve), apparent diffusion coefficient (ADC), the initial area in the signal intensity-time curve (IAUGC), and contrast-enhancement ratio (CER). In addition, a Student's t-test was conducted to calculate statistical significance regarding the quantitatively analyzed perfusion parameters in benign SPLs compared to malignant SPLs. The area under (AUC) the receiver operating characteristic (ROC) curve was studied to investigate the performance of perfusion parameters in diagnosing lung cancer. Values of Ktrans, Kep, Ve, MaxSlope, and IAUGC increased within malignant nodules relative to benign nodules (Ktrans: 0.21 ±0.08 vs. 0.73 ±0.40, P = 0.0001; Kep: 1.21 ±0.66 vs. 1.83 ±0.90, P = 0.0163; Ve: 0.24 ±0.08 vs. 0.47 ±0.18, P < 0.0001; MaxSlope: 0.09 ±0.14 vs. 0.28 ±0.29, P = 0.0166; IAUGC: 0.18 ±0.09 vs. 0.55 ±0.34, P = 0.0001). Meanwhile, malignant nodules presented higher ADC than benign nodules (0.0016 ±0.0006 vs. 0.0012 ±0.0003, P = 0.0019). Ktrans and IAUGC showed the best diagnostic performance with AUCs [1.0, 95%CI (0.99-1.0); 0.93, 95%CI(0.85-1.0), respectively]. Malignant pulmonary lesions had higher values of Ktrans, Ve, Kep, MaxSlope, and IAUGC compared to benign pulmonary lesions. Overall, perfusion parameters of DCE-MRI facilitate discrimination between benign from malignant pulmonary nodules.

P15.04.A BIOLOGICAL CORRELATES OF LEAKAGE EFFECT METRICS COMPUTED FROM DYNAMIC SAGE-EPI MRI IN ENHANCING AND NON-ENHANCING HUMAN GLIOMAS

Abstract BACKGROUND Dynamic spin-and-gradient-echo echoplanar imaging (SAGE-EPI) can be used to compute novel quantitative maps derived from contrast leakage effects, which are thought to reflect tissue characteristics, while acquiring perfusion imaging. In this study, we explored leakage effect metrics and their biological correlates in human gliomas. METHODS 57 patients with histology-proven gliomas were studied (38 enhancing, 19 non-enhancing). The following quantitative leakage effect maps were computed: ΔR2,ss* (reflecting T2*-leakage effects, dependent on cytoarchitecture), ΔR1,ss (reflecting T1-leakage effects, dependent on blood-brain barrier permeability), and the transverse relaxivity at tracer equilibrium (TRATE, reflecting the balance between ΔR2,ss* and ΔR1,ss). In enhancing gliomas, these metrics were compared between patient subgroups (treatment-naïve [TN] vs recurrent [R]) and biological features (IDH status, Ki67 expression). In non-enhancing gliomas, qualitative and quantitative analyses were performed to evaluate the potential usefulness of leakage effects in the absence of gross contrast enhancement. RESULTS In enhancing IDH-wild-type gliomas (IDHwt), previous exposure to treatment determined higher ΔR1,ss (p=0.035) and lower TRATE (p=0.002). In IDH-mutant-gliomas (IDHm), previous treatment determined higher ΔR1,ss (p=0.026). In TN-gliomas, IDHwt status tended to determine higher ΔR1,ss and lower TRATE (p=0.13). ΔR1,ss values were correlated with Ktrans values (TN/R p=0.036/0.0024, r=0.68/0.59). TRATE values above 142 mM-1s-1 were exclusively seen in TN-IDHwt, and in TN-gliomas this cutoff had 89% sensitivity and 80% specificity as a predictor of Ki67&amp;gt;10%. Preliminary analyses on non-enhancing gliomas revealed that a subset of gliomas (n=11) showing a visual tumor-to- BACKGROUND contrast in leakage effect maps were higher in grade (p=0.049), and all grade 4 gliomas (n=2) displayed pronounced leakage effects. CONCLUSION s: In enhancing gliomas novel leakage effect metrics computed with dynamic SAGE-EPI may reflect cytoarchitecture and blood-brain barrier disruption. More in detail, TRATE was higher in IDHwt-gliomas and high-Ki67 gliomas, consistently with the hypothesis of TRATE values being proportional to cell volume fraction and cell size. ΔR1,ss was correlated to Ktrans and higher in IDHwt-gliomas and treated gliomas, consistently with the hypothesis of ΔR1,ss being a potential marker of blood-brain barrier disruption. Preliminary results on non-enhancing gliomas suggest that leakage effect metrics are more likely to be visualized in higher grades, and may be insightful in this subset despite the absence of gross contrast-enhancement. Overall, leakage effect metrics may provide insights regarding tissue characteristics with potential applications in differential diagnosis and treatment response assessment.

The value of dynamic contrast-enhanced MRI in the differentiation between benign and malignant lacrimal epithelial tumors

Objective: To investigate the diagnostic performance of multiparametric dynamic contrast-enhanced MRI(DCE-MRI) for the differentiation between benign and malignant larcrimal gland epithelial tumors. Methods: The clinical and imaging data of 104 patients with epithelial tumors of the lacrimal gland who underwent orbital MRI scan and met the inclusion criteria in Beijing Tongren Hospital from January 2011 to December 2017 were retrospectively collected, including 48 males and 56 females, aged from 12 to 77 (43±7) years. Sixty-three cases of benign epithelial tumors and 41 cases of malignant epithelial tumors were examined by DCE-MRI. The parameters of semiquantitative analysis including: time to peak enhancement (Tpeak), maximum enhancement ratio (ERmax), Slope, washout ratio (WR) and time-signal intensity curve (TIC) types. The parameters of quantitative analysis including: volume transfer constant (Ktrans), the extravascular extracellular volume fraction (Ve) and rate constant (Kep). Receiver operating characteristic (ROC) curve analysis was performed for DCE-MRI parameters with statistically significant differences, the area under the curve (AUC) was calculated, the diagnostic threshold was determined, and the diagnostic performance was evaluated. Logistic regression analysis was used to determine the best parameters for differential diagnosis of benign and malignant epithelial tumors of the lacrimal gland. Results: For the semiquantitative analysis of DCE-MRI, malignant lacrimal gland epithelial tumor had a significantly shorter Tpeak than benign masses [(103.77±57.87) s vs (187.80±77.01) s,P<0.001)], while had a higher value in ERmax, Slope [M(Q1,Q3)] and WR in malignant masses compared with benign one [1.55±0.39 vs 1.36±0.33; 1.76 (0.97,2.27) vs 0.62 (0.50,0.93); 7.70%(1.40%, 21.60%)% vs 0(0, 0),all P<0.05)].The TICs of benign lacrimal tumors mainly showed a persistent type (49/63),while most malignant lacrimal tumors mainly showed a plateau type (25/41). For the quantitative analysis of DCE-MRI, the values of Ktrans and Kep[M(Q1,Q3)] in malignant tumors were significantly greater than those of benign tumors (0.99±0.52/min vs 0.43±0.23/min, P<0.001; 1.33(0.83, 1.55)/min vs 0.55(0.46, 0.68)/min, P<0.001). No significant difference in Ve was found between the groups (0.76±0.20 vs 0.73±0.22,P=0.467). Through the statistical analysis, TIC types (OR=3.887,95%CI: 1.409-10.725) and Ktrans(OR=50.979,95%CI: 6.046-429.830) can provide superior diagnostic performance for predicting malignant lacrimal gland epithelial tumors, with a sensitivity of 78.05%, specificity of 77.78%,and sensitivity of 70.73%, specificity of 95.24%, respevtively. Furthermore, the comprehensive diagnostic performance of Ktrans in AUC was proven to be significantly better than that of TIC [0.875 (0.796-0.932) vs 0.798 (0.708-0.870),P=0.049]. Conclusions: Multiparametric DCE-MRI is helpful for the differential diagnosis of benign and malignant epithelial tumors of lacrimal gland. TIC type and Ktrans have higher diagnostic value, and the diagnostic performance of Ktrans is better than that of TIC.

Dynamic 2-deoxy-D-glucose-enhanced multispectral optoacoustic tomography for assessing metabolism and vascular hemodynamics of breast cancer

Clinical tools for measuring tumor vascular hemodynamics, such as dynamic contrast-enhanced MRI, are clinically important to assess tumor properties. Here we explored the use of multispectral optoacoustic tomography (MSOT), which has a high spatial and temporal resolution, to measure the intratumoral pharmacokinetics of a near-infrared-dye-labeled 2-Deoxyglucose, 2-DG-800, in orthotropic 2-LMP breast tumors in mice. As uptake of 2-DG-800 is dependent on both vascular properties, and glucose transporter activity – a widely-used surrogate for metabolism, we evaluate hemodynamics of 2-DG-MP by fitting the dynamic MSOT signal of 2-DG-800 into two-compartment models including the extended Tofts model (ETM) and reference region model (RRM). We showed that dynamic 2-DG-enhanced MSOT (DGE-MSOT) is powerful in acquiring hemodynamic rate constants, including Ktrans and Kep, via systemically injecting a low dose of 2-DG-800 (0.5 µmol/kg b.w.). In our study, both ETM and RRM are efficient in deriving hemodynamic parameters in the tumor. Area-under-curve (AUC) values (which correlate to metabolism), and Ktrans and Kep values, can effectively distinguish tumor from muscle. Hemodynamic parameters also demonstrated correlations to hemoglobin, oxyhemoglobin, and blood oxygen level (SO2) measurements by spectral unmixing of the MSOT data. Together, our study for the first time demonstrated the capability of DGE-MSOT in assessing vascular hemodynamics of tumors.

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.

Histogram analysis of dynamic contrast-enhanced magnetic resonance imaging to predict extramural venous invasion in rectal cancer

BackgroundTo explore the potential of histogram analysis (HA) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the identification of extramural venous invasion (EMVI) in rectal cancer patients.MethodsThis retrospective study included preoperative images of 194 rectal cancer patients at our hospital between May 2019 and April 2022. The postoperative histopathological examination served as the reference standard. The mean values of DCE-MRI quantitative perfusion parameters (Ktrans, Kep and Ve) and other HA features calculated from these parameters were compared between the pathological EMVI-positive and EMVI-negative groups. Multivariate logistic regression analysis was performed to establish the prediction model for pathological EMVI-positive status. Diagnostic performance was assessed and compared using the receiver operating characteristic (ROC) curve. The clinical usefulness of the best prediction model was further measured with patients with indeterminate MRI-defined EMVI (mrEMVI) score 2(possibly negative) and score 3 (probably positive).ResultsThe mean values of Ktrans and Ve in the EMVI-positive group were significantly higher than those in the EMVI-negative group (P = 0.013 and 0.025, respectively). Significant differences in Ktrans skewness, Ktrans entropy, Ktrans kurtosis, and Ve maximum were observed between the two groups (P = 0.001,0.002, 0.000, and 0.033, respectively). The Ktrans kurtosis and Ktrans entropy were identified as independent predictors for pathological EMVI. The combined prediction model had the highest area under the curve (AUC) at 0.926 for predicting pathological EMVI status and further reached the AUC of 0.867 in subpopulations with indeterminate mrEMVI scores.ConclusionsHistogram Analysis of DCE-MRI Ktrans maps may be useful in preoperative identification of EMVI in rectal cancer, particularly in patients with indeterminate mrEMVI scores.