Contralateral Normal-appearing White Matter Research Articles

Differentiation of hemispheric white matter lesions in migraine and multiple sclerosis with similar radiological features using advanced MRI.

White matter hyperintensities (WMHs), presented on T2-weighted or fluid-attenuated inversion recovery magnetic resonance imaging (MRI) sequences, are lesions in the human brain that can be observed in both migraine and multiple sclerosis (MS). Seventeen migraine patients and 15 patients with relapsing-remitting multiple sclerosis with WMHs, and 17 healthy subjects age-and sex-matched to the migraine group were prospectively enrolled and underwent conventional and advanced MRI studies with diffusion-and perfusion-weighted imaging and single voxel proton magnetic resonance spectroscopy. In both disease groups, elevated T2 relaxation time, apparent diffusion coefficient (ADC) values, and decreased N-acetyl-aspartate levels were found in the intralesional white matter compared to the contralateral normal-appearing white matter (NAWM), while there was no difference between the hemispheres of the control subjects. Migraine patients had the lowest intralesional creatine + phosphocreatine and myo-inositol (mI) values among the three groups, while patients with MS showed the highest intralesional T1 and T2 relaxation times, ADC, and mI values. In the contralateral NAWM, the same trend with mI changes was observed in migraineurs and MS patients. No differences in perfusion variables were observed in any groups. Our multimodal study showed that tissue damage is detectable in both diseases. Despite the differences in various advanced MRI measures, with more severe injury detected in MS lesions, we could not clearly differentiate the two white matter lesion types.

Ultra-high b-value DWI accurately identifies isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas.

To distinguish isocitrate dehydrogenase (IDH) genotypes and tumor subtypes of adult-type diffuse gliomas based on the fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5) in 2021 using standard, high, and ultra-high b-value diffusion-weighted imaging (DWI). This prospective study enrolled 70 patients with adult-type diffuse gliomas who underwent multiple b-value DWI. Apparent diffusion coefficient (ADC) values including ADCb500/b1000, ADCb500/b2000, ADCb500/b3000, ADCb500/b4000, ADCb500/b6000, ADCb500/b8000, and ADCb500/b10000 in tumor parenchyma (TP) and contralateral normal-appearing white matter (NAWM) were calculated. The ADC ratios of TP/NAWM were assessed for correlations with IDH genotypes, tumor subtypes, and Ki-67 status; diagnostic performances were compared. All ADCs were significantly higher in IDHmutant gliomas than in IDH wild-type gliomas (p < 0.01 for all); ADCb500/b8000 had the highest area under the curve (AUC) of 0.866. All ADCs were significantly lower in glioblastoma than in astrocytoma (p < 0.01 for all). ADCs other than ADCb500/b1000 were significantly lower in glioblastoma than in oligodendroglioma (p < 0.05 for all). ADCb500/b8000 and ADCb500/b10000 were significantly higher in oligodendroglioma than in astrocytoma (p = 0.034 and 0.023). The highest AUCs were 0.818 for ADCb500/b6000 when distinguishing glioblastoma from astrocytoma, 0.979 for ADCb500/b8000 and ADCb500/b10000 when distinguishing glioblastoma from oligodendroglioma, and 0.773 for ADCb500/b10000 when distinguishing astrocytoma from oligodendroglioma. Additionally, all ADCs were negatively correlated with Ki-67 status (p < 0.05 for all). Ultra-high b-value DWI can reliably separate IDH genotypes and tumor subtypes of adult-type diffuse gliomas using WHO CNS5 criteria. Ultra-high b-value diffusion-weighted imaging can accurately distinguish isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas, which may facilitate personalized treatment and prognostic assessment for patients with glioma. • Ultra-high b-value diffusion-weighted imaging can accurately distinguish subtle differences in water diffusion among biological tissues. • Ultra-high b-value diffusion-weighted imaging can reliably separate isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas. • Compared with standard b-value diffusion-weighted imaging, high and ultra-high b-value diffusion-weighted imaging demonstrate better diagnostic performances.

Prognostic Value of Apparent Diffusion Coefficient (ADC) in Patients with Diffuse Gliomas.

This study aimed to evaluate potential posttreatment changes in ADC values within the tissue surrounding the enhancing lesion, particularly in areas not exhibiting MRI characteristics of involvement. Additionally, the objective was to investigate the correlations among ADC values, treatment response, and survival outcomes in individuals diagnosed with gliomas. This retrospective study included a total of 49 patients that underwent either stereotactic biopsy or maximal surgical resection. Histologically confirmed as Grade III or IV gliomas, all cases adhered to the 2016 and 2021 WHO classifications, with subsequent radio-chemotherapy administered post-surgery. Patients were divided into two groups: short and long survival groups. Baseline and follow-up MRI scans were obtained on a 1.5 T MRI scanner. Two ROI circles were positioned near the enhancing area, one ROI in the NAWM ipsilateral to the neoplasm and another symmetrically in the contralateral hemisphere on ADC maps. At follow-up there was a significant difference in both ipsilateral and contralateral NAWM between the two groups, -0.0857 (p = 0.004) and -0.0607 (p = 0.037), respectively. There was a weak negative correlation between survival and ADC values in ipsilateral and contralateral NAWM at the baseline with the correlation coefficient -0.328 (p = 0.02) and -0.302 (p = 0.04), respectively. The correlation was stronger at the follow-up. The findings indicate that ADC values in normal-appearing white matter (NAWM) may function as a prognostic biomarker in patients with diffuse gliomas.

Probing the glioma microvasculature: a case series of the comparison between perfusion MRI and intraoperative high-frame-rate ultrafast Doppler ultrasound

BackgroundWe aimed to describe the microvascular features of three types of adult-type diffuse glioma by comparing dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI) with intraoperative high-frame-rate ultrafast Doppler ultrasound.MethodsCase series of seven patients with primary brain tumours underwent both DSC perfusion MRI and intra-operative high-frame-rate ultrafast Doppler ultrasound. From the ultrasound images, three-dimensional vessel segmentation was obtained of the tumour vascular bed. Relative cerebral blood volume (rCBV) maps were generated with leakage correction and normalised to the contralateral normal-appearing white matter. From tumour histograms, median, mean, and maximum rCBV ratios were extracted.ResultsLow-grade gliomas (LGGs) showed lower perfusion than high-grade gliomas (HGGs), as expected. Within the LGG subgroup, oligodendroglioma showed higher perfusion than astrocytoma. In HGG, the median rCBV ratio for glioblastoma was 3.1 while astrocytoma grade 4 showed low perfusion with a median rCBV of 1.2. On the high-frame-rate ultrafast Doppler ultrasound images, all tumours showed a range of rich and organised vascular networks with visually apparent abnormal vessels, even in LGG.ConclusionsThis unique case series revealed in vivo insights about the microvascular architecture in both LGGs and HGGs. Ultrafast Doppler ultrasound revealed rich vascularisation, also in tumours with low perfusion at DSC MRI. These findings warrant further investigations using advanced MRI postprocessing, in particular for characterising adult-type diffuse glioma.Relevance statementOur findings challenge the current assumption behind the estimation of relative cerebral blood volume that the distribution of blood vessels in a voxel is random.Key points• Ultrafast Doppler ultrasound revealed rich vascularity irrespective of perfusion dynamic susceptibility contrast MRI state.• Rich and organised vascularisation was also observed even in low-grade glioma.• These findings challenge the assumptions for cerebral blood volume estimation with MRI.Graphical

Paediatric supratentorial tumours do not cause microstructural alterations in contralateral white matter: a preliminary study.

Intracranial tumours in children can exhibit different characteristics compared to those in adults. Understanding the microstructural changes in the contralateral normal-appearing white matter (NAWM) in children with primary intracranial masses is essential for optimizing treatment strategies. This study aimed to investigate the apparent diffusion coefficient (ADC) changes in contralateral NAWM using fully automated methods and deep learning algorithms. We included 22 paediatric patients with primary supratentorial intracranial masses (23% high-grade) in the study. ADC values of the contralateral NAWM in the patient group were compared to those of a control group. Deep learning algorithms were utilized to analyse diffusion changes in NAWM. The mean ADC values of contralateral NAWM in the patient group were 0.80 ± 0.03 × 10-3 mm2/s, while the control group had a mean ADC value of 0.81 ± 0.03 × 10-3 mm2/s. There was no statistically significant difference between the groups (p = 0.39). Our findings indicate that there are no significant diffusion changes in the contralateral white matter of children with supratentorial intracranial masses. Primary supratentorial intracranial masses in children do not cause microstructural changes in contralateral normal-appearing white matter. This could be attributed to the less infiltrative nature and different biochemical profile of these tumour groups in the paediatric population. Further studies using advanced imaging techniques could provide additional insights into the distinct characteristics of paediatric intracranial tumours and improve patient management.

CEST 2022 - Differences in APT-weighted signal in T1 weighted isointense lesions, black holes and normal-appearing white matter in people with relapsing-remitting multiple sclerosis

PurposeTo evaluate amide proton transfer weighted (APTw) signal differences between multiple sclerosis (MS) lesions and contralateral normal-appearing white matter (cNAWM). Cellular changes during the demyelination process were also assessed by comparing APTw signal intensity in T1weighted isointense (ISO) and hypointense (black hole -BH) MS lesions in relation to cNAWM. MethodsTwenty-four people with relapsing-remitting MS (pw-RRMS) on stable therapy were recruited. MRI/APTw acquisitions were undertaken on a 3 T MRI scanner. The pre and post-processing, analysis, co-registration with structural MRI maps, and identification of regions of interest (ROIs) were all performed with Olea Sphere 3.0 software. Generalized linear model (GLM) univariate ANOVA was undertaken to test the hypotheses that differences in mean APTw were entered as dependent variables. ROIs were entered as random effect variables, which allowed all data to be included. Regions (lesions and cNAWM) and/or structure (ISO and BH) were the main factor variables. The models also included age, sex, disease duration, EDSS, and ROI volumes as covariates. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic performance of these comparisons. ResultsA total of 502 MS lesions manually identified on T2-FLAIR from twenty-four pw-RRMS were subcategorized as 359 ISO and 143 BH with reference to the T1-MPRAGE cerebral cortex signal. Also, 490 ROIs of cNAWM were manually delineated to match the MS lesion positions. A two-tailed t-test showed that mean APTw values were higher in females than in males (t = 3.52, p < 0.001). Additionally, the mean APTw values of MS lesions were higher than those of cNAWM after accounting for covariates (mean lesion = 0.44, mean cNAWM = 0.13, F = 44.12, p < 0.001).The mean APTw values of ISO lesions were higher than those of cNAWM after accounting for covariates (mean ISO lesions = 0.42, mean cNAWM = 0.21, F = 12.12, p < 0.001). The mean APTw values of BH were also higher than those of cNAWM (mean BH lesions = 0.47, mean cNAWM = 0.033, F = 40.3, p < 0.001). The effect size (i.e., difference between lesion and cNAWM) for BH was found to be higher than for ISO (14 vs. 2).Diagnostic performance showed that APT was able to discriminate between all lesions and cNAWM with an accuracy of >75% (AUC = 0.79, SE = 0.014). Discrimination between ISO lesions and cNAWM was accomplished with an accuracy of >69% (AUC = 0.74, SE = 0.018), while discrimination between BH lesions and cNAWM was achieved at an accuracy of >80% (AUC = 0.87, SE = 0.021). ConclusionsOur results highlight the potential of APTw imaging for use as a non-invasive technique that is able to provide essential molecular information to clinicians and researchers so that the stages of inflammation and degeneration in MS lesions can be better characterized.

Blood-Brain Barrier Permeability and Kinetics of Inflammatory Markers in Acute Stroke Patients Treated With Thrombectomy.

The aim of this study was to investigate the relationship between baseline blood-brain barrier (BBB) permeability and the kinetics of circulating inflammatory markers in a cohort of acute ischemic stroke (AIS) patients treated with mechanical thrombectomy. The CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke includes AIS patients treated with mechanical thrombectomy after admission MRI and undergoing a sequential assessment of circulating inflammatory markers. Baseline dynamic susceptibility perfusion MRI was postprocessed with arrival time correction to provide K2 maps reflecting BBB permeability. After coregistration of apparent diffusion coefficient and K2 maps, the 90th percentile of K2 value was extracted within baseline ischemic core and expressed as a percentage change compared with contralateral normal-appearing white matter. Population was dichotomized according to the median K2 value. Univariable and multiple variable logistic regression analyses were performed to investigate factors associated with increased pretreatment BBB permeability in the whole population and in patients with symptom onset <6 hours. In the whole population (n = 105 patients, median K2 = 1.59), patients with an increased BBB permeability had higher serum levels of matrix metalloproteinase (MMP)-9 at H48 (p = 0.02), a higher C-reactive protein (CRP) serum level at H48 (p = 0.01), poorer collateral status (p = 0.01), and a larger baseline ischemic core (p < 0.001). They were more likely to have hemorrhagic transformation (p = 0.008), larger final lesion volume (p = 0.02), and worst neurologic outcome at 3 months (p = 0.04). The multiple variable logistic regression indicated that an increased BBB permeability was associated only with ischemic core volume (odds ratio [OR] 1.04, 95% CI 1.01-1.06, p < 0.0001). Restricting analysis to patients with symptom onset <6 hours (n = 72, median K2 = 1.27), participants with an increased BBB permeability had higher serum levels of MMP-9 at H0 (p = 0.005), H6 (p = 0.004), H24 (p = 0.02), and H48 (p = 0.01), higher CRP levels at H48 (p = 0.02), and a larger baseline ischemic core (p < 0.0001). The multiple variable logistic analysis showed that increased BBB permeability was independently associated with higher H0 MMP-9 levels (OR 1.33, 95% CI 1.12-1.65, p = 0.01) and a larger ischemic core (OR 1.27, 95% CI 1.08-1.59, p = 0.04). In AIS patients, increased BBB permeability is associated with a larger ischemic core. In the subgroup of patients with symptom onset <6 hours, increased BBB permeability is independently associated with higher H0 MMP-9 levels and a larger ischemic core.

The Consistence of Dynamic Contrast-Enhanced MRI and Filter-Exchange Imaging in Measuring Water Exchange Across the Blood-Brain Barrier in High-Grade Glioma.

Water exchange across blood-brain barrier (BBB) (WEXBBB ) is an emerging biomarker of BBB dysfunction with potential applications in many brain diseases. Several MRI methods have been proposed to measure WEXBBB , but evidence remains scarce whether different methods can produce comparable WEXBBB . To explore whether dynamic contrast-enhanced (DCE)-MRI and vascular water exchange imaging (VEXI) could produce comparable WEXBBB in high-grade glioma (HGG) patients. Prospective cross-sectional. 13 HGG patients (58.4 ± 9.4 years, 9 females, 4 WHO III and 9 WHO IV). A 3 T, spoiled gradient-recalled-echo DCE-MRI and VEXI containing two pulsed-gradient spin-echo blocks separated by a mixing block. The enhanced tumor and contralateral normal-appearing white matter (cNAWM) volume-of-interests (VOIs) were drew by two neuroradiologists. And whole-brain NAWM and normal-appearing gray matter (NAGM) without tumor-affected regions were segmented by automated segmentation algorithm in FSL. Student's t-test was used to evaluate parameters difference between cNAWM and tumor, NAGM and NAWM, respectively. The correlation between vascular water efflux rate constant (kbo ) from DCE-MRI and apparent exchange rate across BBB (AXRBBB ) from VEXI was evaluated by Pearson correlation. P < 0.05 was considered statistically significant. Compared with cNAWM, both kbo and AXRBBB were significantly reduced in tumor (kbo = 3.50 ± 1.18 sec-1 vs. 1.03 ± 0.75 sec-1 ; AXRBBB = 3.54 ± 1.11 sec-1 vs. 1.94 ± 1.04 sec-1 ). Both kbo and AXRBBB showed significantly higher values in NAWM than NAGM (kbo = 3.50 ± 0.59 sec-1 vs. 2.10 ± 0.56 sec-1 ; AXRBBB = 3.35 ± 0.77 sec-1 vs. 2.07 ± 0.52 sec-1 ). The VOI-averaged kbo and AXRBBB were also linearly correlated in tumor, NAWM, and NAGM (r = 0.59). DCE-MRI and VEXI showed comparable and correlated WEXBBB in HGG patients, suggesting that the consistence and reliability of these two MRI methods in measuring WEXBBB . 2. Stage 1.

Amide Proton Transfer Imaging for Differentiation of Glioblastoma from Brain Metastasis

Objective: To evaluate the difference in amide proton transfer (APT)-weighted imaging between glioblastoma and brain metastasis. Materials and Methods: Fourteen patients including eight males and six females, with age ranging between 46 and 75 years old, were included in the present study. Ten patients with glioblastomas and four patients with brain metastases underwent preoperative brain 3T-MRI with APT-weighted sequence. The magnetization transfer ratio asymmetry (MTRasym) and normalized magnetization transfer ratio asymmetry (nMTRasym) values in enhancing solid portion, peritumoral non-enhancing hyperintense FLAIR area, and contralateral normal appearing white matter (CNAWM) in glioblastomas and brain metastases were obtained and compared for statistical analyses. Final diagnosis was validated by pathological results. Results: The MTRasym and nMTRasym in enhancing solid portion and peritumoral non-enhancing hyperintense FLAIR area of glioblastomas were significantly greater than that of the brain metastases. By visual assessment, the APTw color map also showed higher signal at the perilesional edema in glioblastomas than the metastasis. Conclusion: As a non-invasive imaging method, APT-weighted MR imaging might be helpful to distinguish glioblastomas from brain metastasis. Keywords: Amide proton transfer weighted imaging; Glioblastomas; Brain metastasis

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

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. 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). 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. 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.

Evaluation of white matter microstructure in pediatric onset multiple sclerosis with diffusion compartment imaging.

Pediatric-onset multiple sclerosis (POMS) shows earlier axonal involvement and greater axonal loss than in adults. We aim to characterize the white matter (WM) microstructural changes in POMS using a diffusion compartment imaging (DCI) model and compare it to standard diffusion tensor imaging (DTI). Eleven patients (2 males, mean age 18.8±3.9years) with a diagnosis of relapsing and remitting POMS (mean age at disease onset 13.8±2.9years, mean duration 5.1±1.9years) and healthy controls (8 males, mean age 26.4±6.5years) were recruited and imaged at 3T. A 90-gradient set Cube and Sphere acquisition and a novel DCI model known as DIstribution of Anisotropic MicrOstructural eNvironments with Diffusion-weighted imaging (DIAMOND) were used to calculate a single anisotropic compartment, an isotropic compartment, and a free diffusion compartment. Lesions and contralateral normal-appearing white matter (NAWM) in patients and whole brain WM for controls were labeled. Eleven patients and 11 controls were recruited. When comparing lesions and contralateral NAWM in patients using DCI, compartmental axial diffusivity, radial diffusivity (cRD), and mean diffusivity (cMD) were higher in lesions. Conversely, compartmental fractional anisotropy (cFA) and heterogeneity index were lower in lesions. An analysis of DTI equivalents showed the same trends. In whole-brain NAWM of patients compared to controls, cRD and cMD were higher and cFA was lower in patients. Lesions in POMS can be accurately characterized by a DCI model. Incipient changes in NAWM seen in DCI may not be readily observable by DTI.

3D Amide Proton Transfer Weighted Brain Tumor Imaging With Compressed SENSE: Effects of Different Acceleration Factors.

ObjectivesThe aim of the current study was to evaluate the performance of compressed SENSE (CS) for 3D amide proton transfer weighted (APTw) brain tumor imaging with different acceleration factors (AFs), and the results were compared with those of conventional SENSE.MethodsApproximately 51 patients with brain tumor (22 males, 49.95 ± 10.52 years) with meningiomas (n = 16), metastases (n = 12), or gliomas (n = 23) were enrolled. All the patients received 3D APTw imaging scans on a 3.0 T scanner with acceleration by CS (AFs: CS2, CS3, CS4, and CS5) and SENSE (AF: S1.6). Two readers independently and subjectively evaluated the APTw images relative to image quality and measured confidence concerning image blur, distortion, motion, and ghosting artifacts, lesion recognition, and contour delineation with a 5-point Likert scale. Mean amide proton transfer (APT) values of brain tumors (APTtumor), the contralateral normal-appearing white matter (APTCNAWM), and the peritumoral edema area (if present, APTedema) and the tumor volume (VAPT) were measured for objective evaluation and determination of the optimal AF. The Ki67 labeling index was also measured by using standard immunohistochemical staining procedures in samples from patients with gliomas, and the correlation between tumor APT values and the Ki67 index was analyzed.ResultsThe image quality of AF = CS5 was significantly lower than that of other groups. VAPT showed significant differences among the six sequences in meningiomas (p = 0.048) and gliomas (p = 0.023). The pairwise comparison showed that the VAPT values of meningiomas measured from images by CS5 were significantly lower, and gliomas were significantly larger than those by SENSE1.6 and other CS accelerations, (p < 0.05). APTtumor (p = 0.191) showed no significant difference among the three types of tumors. The APTtumor values of gliomas measured by APTw images with the SENSE factor of 1.6 and the CS factor of 2, 3, and 4 (except for CS5) were all positively correlated with Ki67.ConclusionCompressed SENSE could be successfully extended to accelerated 3D APTw imaging of brain tumors without compromising image quality using the AF of 4.

Separating Glioma Hyperintensities From White Matter by Diffusion-Weighted Imaging With Spherical Tensor Encoding.

BackgroundTumor-related hyperintensities in high b-value diffusion-weighted imaging (DWI) are radiologically important in the workup of gliomas. However, the white matter may also appear as hyperintense, which may conflate interpretation.PurposeTo investigate whether DWI with spherical b-tensor encoding (STE) can be used to suppress white matter and enhance the conspicuity of glioma hyperintensities unrelated to white matter.Materials and MethodsTwenty-five patients with a glioma tumor and at least one pathology-related hyperintensity on DWI underwent conventional MRI at 3 T. The DWI was performed both with linear and spherical tensor encoding (LTE-DWI and STE-DWI). The LTE-DWI here refers to the DWI obtained with conventional diffusion encoding and averaged across diffusion-encoding directions. Retrospectively, the differences in contrast between LTE-DWI and STE-DWI, obtained at a b-value of 2,000 s/mm2, were evaluated by comparing hyperintensities and contralateral normal-appearing white matter (NAWM) both visually and quantitatively in terms of the signal intensity ratio (SIR) and contrast-to-noise ratio efficiency (CNReff).ResultsThe spherical tensor encoding DWI was more effective than LTE-DWI at suppressing signals from white matter and improved conspicuity of pathology-related hyperintensities. The median SIR improved in all cases and on average by 28%. The median (interquartile range) SIR was 1.9 (1.6 – 2.1) for STE and 1.4 (1.3 – 1.7) for LTE, with a significant difference of 0.4 (0.3 –0.5) (p < 10–4, paired U-test). In 40% of the patients, the SIR was above 2 for STE-DWI, but with LTE-DWI, the SIR was below 2 for all patients. The CNReff of STE-DWI was significantly higher than of LTE-DWI: 2.5 (2 – 3.5) vs. 2.3 (1.7 – 3.1), with a significant difference of 0.4 (−0.1 –0.6) (p < 10–3, paired U-test). The STE improved CNReff in 70% of the cases. We illustrate the benefits of STE-DWI in three patients, where STE-DWI may facilitate an improved radiological description of tumor-related hyperintensity, including one case that could have been missed out if only LTE-DWI was inspected.ConclusionThe contrast mechanism of high b-value STE-DWI results in a stronger suppression of white matter than conventional LTE-DWI, and may, therefore, be more sensitive and specific for assessment of glioma tumors and DWI-hyperintensities.

The Value of APTw CEST MRI in Routine Clinical Assessment of Human Brain Tumor Patients at 3T.

Background. With fast-growing evidence in literature for clinical applications of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI), this prospective study aimed at applying amide proton transfer-weighted (APTw) CEST imaging in a clinical setting to assess its diagnostic potential in differentiation of intracranial tumors at 3 tesla (T). Methods. Using the asymmetry magnetization transfer ratio (MTRasym) analysis, CEST signals were quantitatively investigated in the tumor areas and in a similar sized region of the normal-appearing white matter (NAWM) on the contralateral hemisphere of 27 patients with intracranial tumors. Area under curve (AUC) analyses were used and results were compared to perfusion-weighted imaging (PWI). Results. Using APTw CEST, contrast-enhancing tumor areas showed significantly higher APTw CEST metrics than contralateral NAWM (AUC = 0.82; p < 0.01). In subgroup analyses of each tumor entity vs. NAWM, statistically significant effects were yielded for glioblastomas (AUC = 0.96; p < 0.01) and for meningiomas (AUC = 1.0; p < 0.01) but not for lymphomas as well as metastases (p > 0.05). PWI showed results comparable to APTw CEST in glioblastoma (p < 0.01). Conclusions. This prospective study confirmed the high diagnostic potential of APTw CEST imaging in a routine clinical setting to differentiate brain tumors.

3D pCASL-perfusion in preoperative assessment of brain gliomas in large cohort of patients

The aim of the study was to evaluate the role of pseudocontinuous arterial spin labeling perfusion (pCASL-perfusion) in preoperative assessment of cerebral glioma grades. The study group consisted of 253 patients, aged 7–78 years with supratentorial gliomas (65 low-grade gliomas (LGG), 188 high-grade gliomas (HGG)). We used 3D pCASL-perfusion for each patient in order to calculate the tumor blood flow (TBF). We obtained maximal tumor blood flow (maxTBF) in small regions of interest (30 ± 10 mm2) and then normalized absolute maximum tumor blood flow (nTBF) to that of the contralateral normal-appearing white matter of the centrum semiovale. MaxTBF and nTBF values significantly differed between HGG and LGG groups (p < 0.001), as well as between patient groups separated by the grades (grade II vs. grade III) (p < 0.001). Moreover, we performed ROC-analysis which demonstrated high sensitivity and specificity in differentiating between HGG and LGG. We found significant differences for maxTBF and nTBF between grade III and IV gliomas, however, ROC-analysis showed low sensitivity and specificity. We did not observe a significant difference in TBF for astrocytomas and oligodendrogliomas. Our study demonstrates that 3D pCASL-perfusion as an effective diagnostic tool for preoperative differentiation of glioma grades.

Mean apparent propagator-MRI in evaluation of glioma grade, cellular proliferation, and IDH-1 gene mutation status.

To evaluate the glioma grade, Ki-67 expression, and IDH-1 mutation status using mean apparent propagator (MAP) MRI. Forty enrolled glioma patients underwent structural and diffusion MRI. The diffusion metric values including fractional anisotropy (FA), mean diffusivity (MD), mean squared displacement (MSD), q-space inverse variance (QIV), return-to-origin probability (RTOP), return-to-axis probability (RTAP), and return-to-plane probability (RTPP) in tumor parenchyma (TP) and contralateral normal-appearing white matter (NAWM) were calculated. The TP/NAWM ratios of diffusion metric values were correlated with tumor grades, Ki-67, and IDH-1 mutation statuses, and the diagnostic performance was assessed. QIV were significantly higher, whereas RTAP and RTOP were significantly lower in low-grade gliomas (LGGs) than those in high-grade gliomas (HGGs); QIV and MD were significantly higher, whereas RTAP and RTOP were significantly lower in lower-grade gliomas (grade II and III) than those in grade IV gliomas (p < 0.05 for all). RTAP performed best in grading gliomas. MSD, QIV, and MD were significantly higher, whereas RTAP, RTOP, RTPP, and FA were significantly lower in the IDH-1 mutant gliomas than those in the IDH-1 wild-type ones both for all gliomas and lower-grade gliomas (p < 0.05 for all). RTAP performed best in all gliomas, while QIV performed best in lower-grade gliomas. Additionally, RTAP, RTOP, and FA correlated positively, whereas MSD, QIV, and MD correlated negatively with Ki-67 (p < 0.05 for all). MAP-MRI is a potent approach in evaluating the microstructural changes in gliomas with different grades, cellular proliferation, and IDH-1 mutation statuses. • MAP-MRI, a newly developed diffusion technique, accurately reveals microstructure-related features in the complex white matter by recovering important microstructural tissue parameters. • MAP-MRI is a potent approach in evaluating the glioma grade, IDH-1 mutation status, and Ki-67 expression. • Compared with DTI, MAP-MRI seems to demonstrate higher diagnostic performance.

Evaluation of normal-appearing white matter with perfusion and diffusion MRI in patients with treated glioblastoma.

We tried to reveal how the normal appearing white matter (NAWM) was affected in patients with glioblastoma treated with chemo-radiotherapy (CRT) in the period following the treatment, by multiparametric MRI. 43 multiparametric MRI examinations of 17 patients with glioblastoma treated with CRT were examined. A total of six different series or maps were analyzed in the examinations: Apparent Diffusion Coefficient (ADC) and Fractional Anisotropy (FA) maps, Gradient Echo (GRE) sequence, Dynamic susceptibility contrast (DSC) and Arterial spin labeling (ASL) perfusion sequences. Each sequence in each examination was examined in detail with 14 Region of Interest (ROI) measurements. The obtained values were proportioned to the contralateral NAWM values and the results were recorded as normalized values. Time dependent changes of normalized values were statistically analyzed. The most prominent changes in follow-up imaging occurred in the perilesional region. In perilesional NAWM, we found a decrease in normalized FA (nFA), rCBV (nrCBV), rCBF (nrCBF), ASL (nASL)values (p < 0.005) in the first 3 months after treatment, followed by a plateau and an increase approaching pretreatment values, although it did not reach. Similar but milder findings were present in other NAWM areas. In perilesional NAWM, nrCBV values were found to be positively high correlated with nrCBF and nASL, and negatively high correlated with nADC values (r: 0.963, 0.736, - 0.973, respectively). We also found high correlations between the mean values of nrCBV, nrCBF, nASL in other NAWM areas (r: 0.891, 0.864, respectively). We showed that both DSC and ASL perfusion values decreased correlatively in the first 3 months and showed a plateau after 1 year in patients with glioblastoma treated with CRT, unlike the literature. Although it was not as evident as perfusion MRI, it was observed that the ADC values also showed a plateau pattern following the increase in the first 3 months. Further studies are needed to explain late pathophysiological changes. Because of the high correlation, our results support ASL perfusion instead of contrast enhanced perfusion methods.

Fast and equilibrium CEST imaging of brain tumor patients at 3T

Chemical exchange saturation transfer (CEST) MRI, versatile for detecting endogenous mobile proteins and tissue pH, has proved valuable in tumor imaging. However, CEST MRI scans are often performed under non-equilibrium conditions, which confound tissue characterization. This study proposed a quasi-steady-state (QUASS) CEST MRI algorithm to standardize fast and accurate tumor imaging at 3 T. The CEST signal evolution was modeled by longitudinal relaxation rate during relaxation delay (Td) and spinlock relaxation during RF saturation time (Ts), from which the QUASS CEST effect is derived. Numerical simulation and human MR imaging experiments (7 healthy volunteers and 19 tumor patients) were conducted at 3 T to compare the CEST measurements obtained under two representative experimental conditions. In addition, amide proton transfer (APT), combined magnetization transfer (MT) and nuclear overhauser enhancement (NOE) effects, and direct water saturation were isolated using a 3-pool Lorentzian fitting in white matter and gray matter of healthy volunteers and for patients in the contralateral normal-appearing white matter and tumor regions. Finally, the student's t-test was performed between conventional and QUASS CEST measurements. The routine APT and combined MT & NOE measures significantly varied with Ts and Td (P < .001) and were significantly smaller than the corresponding QUASS indices (P < .001). In contrast, the results from the QUASS reconstruction showed little dependence on the scan protocol (P > .05), indicating the accuracy and robustness of QUASS CEST MRI for tumor imaging. To summarize, the QUASS CEST reconstruction algorithm enables fast and accurate tumor CEST imaging at 3 T, promising to expedite and standardize clinical CEST MRI.

NIMG-21. VARIABLE RESOLUTION HYPERPOLARIZED [2-13C]PYRUVATE MRI IN HEALTHY VOLUNTEERS AND PATIENTS WITH IDH-MUTANT GLIOMA

Abstract INTRODUCTION Mutations in isocitrate dehydrogenase (IDH) have been investigated as a prognostic biomarker in glioma. The presence of the IDH mutation (IDHm) is associated with 2-hydroxyglutarate (2HG) production and inhibition of glutamate synthesis (McBrayer, Cell 2018). Hyperpolarized carbon-13 (HP-13C) MRI enables dynamic measurements of in-vivo metabolism using a [2-13C]pyruvate labeled probe that undergoes conversion to [2-13C]lactate and [5-13C]glutamate. Here, we present HP [2-13C]pyruvate data from healthy volunteers and patients with IDHm diffuse glioma. Due to its intrinsic low signal-to-noise ratio (SNR), we demonstrate the ability of post-processing denoising to improve its utility and aid in detection of metabolic changes associated with IDHm. METHODS Dynamic HP 13C data were acquired following intravenous injection of [2-13C]pyruvate from five healthy volunteers and one patient with IDHm grade III astrocytoma. A novel multi-resolution frequency specific multislice EPI sequence was used to obtain [2-13C]pyruvate, [5-13C]glutamate, and downfield and upfield [2-13C]lactate signals (3s temporal resolution, pyruvate/lactate/glutamate spatial resolutions = 0.75x0.75cm2/ 2.25x2.25cm2/ 2.25x2.25cm2, 5 slices 3cm thick). Following phase correction, patch-based tensor decomposition denoising was applied to metabolite images. Metabolite differences between normal-appearing white matter (NAWM) and T2 lesion were examined for the patient data. RESULTS HP [2-13C]pyruvate imaging is able to simultaneously probe glycolytic ([2-13C]lactate) and oxidative ([5-13C]glutamate) metabolism. Denoised pyruvate/lactate/glutamate signals achieved a 4-9/3-6/3-7 fold increase in SNR. T2 lesion exhibited decreased glutamate-to-pyruvate and glutamate-to-lactate AUC ratios versus contralateral NAWM (p&amp;lt; 0.018, p &amp;lt; 1.5e-5), consistent with IDH mutant status. CONCLUSION We successfully demonstrated the feasibility of applying variable resolution HP [2-13C]pyruvate metabolic imaging to detect IDHm specific metabolism. This technique addresses a major hurdle in HP 13C MRI by improving SNR while permitting robust metabolism quantification. Future studies will optimize methods for acquiring and processing data to evaluate further data acquired from IDHm glioma patients. Supported by NIH T32 CA151022, P01 CA118816, and NICO.

Abnormalities in normal-appearing white matter from which multiple sclerosis lesions arise.

Normal-appearing white matter is far from normal in multiple sclerosis; little is known about the precise pathology or spatial pattern of this alteration and its relation to subsequent lesion formation. This study was undertaken to evaluate normal-appearing white matter abnormalities in brain areas where multiple sclerosis lesions subsequently form, and to investigate the spatial distribution of normal-appearing white matter abnormalities in persons with multiple sclerosis. Brain MRIs of pre-lesion normal-appearing white matter were analysed in participants with new T2 lesions, pooled from three clinical trials: SYNERGY (NCT01864148; n = 85 with relapsing multiple sclerosis) was the test data set; ASCEND (NCT01416181; n = 154 with secondary progressive multiple sclerosis) and ADVANCE (NCT00906399; n = 261 with relapsing-remitting multiple sclerosis) were used as validation data sets. Focal normal-appearing white matter tissue state was analysed prior to lesion formation in areas where new T2 lesions later formed (pre-lesion normal-appearing white matter) using normalized magnetization transfer ratio and T2-weighted (nT2) intensities, and compared with overall normal-appearing white matter and spatially matched contralateral normal-appearing white matter. Each outcome was analysed using linear mixed-effects models. Follow-up time (as a categorical variable), patient-level characteristics (including treatment group) and other baseline variables were treated as fixed effects. In SYNERGY, nT2 intensity was significantly higher, and normalized magnetization transfer ratio was lower in pre-lesion normal-appearing white matter versus overall and contralateral normal-appearing white matter at all time points up to 24 weeks before new T2 lesion onset. In ASCEND and ADVANCE (for which normalized magnetization transfer ratio was not available), nT2 intensity in pre-lesion normal-appearing white matter was significantly higher compared to both overall and contralateral normal-appearing white matter at all pre-lesion time points extending up to 2 years prior to lesion formation. In all trials, nT2 intensity in the contralateral normal-appearing white matter was also significantly higher at all pre-lesion time points compared to overall normal-appearing white matter. Brain atlases of normal-appearing white matter abnormalities were generated using measures of voxel-wise differences in normalized magnetization transfer ratio of normal-appearing white matter in persons with multiple sclerosis compared to scanner-matched healthy controls. We observed that overall spatial distribution of normal-appearing white matter abnormalities in persons with multiple sclerosis largely recapitulated the anatomical distribution of probabilities of T2 hyperintense lesions. Overall, these findings suggest that intrinsic spatial properties and/or longstanding precursory abnormalities of normal-appearing white matter tissue may contribute to the risk of autoimmune acute demyelination in multiple sclerosis.