Reproducibility of 3 T APT-CEST in Healthy Volunteers and Patients With Brain Glioma.

BACKGROUND: Amide proton transfer (APT) imaging is a chemical exchange saturation transfer (CEST) technique offering potential clinical applications such as diagnosis, characterization, and treatment planning and monitoring in glioma patients. While APT-CEST has demonstrated high potential, reproducibility remains underexplored. PURPOSE: To investigate whether cerebral APT-CEST with clinically feasible scan time is reproducible in healthy tissue and glioma for clinical use at 3 T. STUDY TYPE: Prospective, longitudinal. SUBJECTS: Twenty-one healthy volunteers (11 females; mean age ± SD: 39 ± 11 years) and 6 glioma patients (3 females; 50 ± 17 years: 4 glioblastomas, 1 oligodendroglioma, 1 radiologically suspected low-grade glioma). FIELD STRENGTH/SEQUENCE: 3 T, Turbo Spin Echo - ampling perfection with application optimized contrasts using different flip angle evolution - chemical exchange saturation transfer (TSE SPACE-CEST). ASSESSMENT: APT-CEST measurement reproducibility was assessed within-session (glioma patients, scan session 1; healthy volunteers scan sessions 1, 2, and 3), between-sessions (healthy volunteers scan sessions 1 and 2), and between-days (healthy volunteers, scan sessions 1 and 3). The mean APTCEST values and standard deviation of the within-subject difference (SDdiff ) were calculated in whole tumor enclosed by regions of interest (ROIs) in patients, and eight ROIs in healthy volunteers-whole-brain, cortical gray matter, putamen, thalami, orbitofrontal gyri, occipital lobes, central brain-and compared. STATISTICAL TESTS: Brown-Forsythe tests and variance component analysis (VCA) were used to assess the reproducibility of ROIs for the three time intervals. Significance was set at P < 0.003 after Bonferroni correction. RESULTS: Intratumoral mean APTCEST was significantly higher than APTCEST in healthy-appearing tissue in patients (0.5 ± 0.46%). The average within-session, between-sessions, and between-days SDdiff of healthy control brains was 0.2% and did not differ significantly with each other (0.76 > P > 0.22). The within-session SDdiff of whole-brain was 0.2% in both healthy volunteers and patients, and 0.21% in the segmented tumor. VCA showed that within-session factors were the most important (60%) for scanning variance. DATA CONCLUSION: Cerebral APT-CEST imaging may show good scan-rescan reproducibility in healthy tissue and tumors with clinically feasible scan times at 3 T. Short-term measurement effects may be the dominant components for reproducibility. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Reliability of brain atrophy measurements in multiple sclerosis using MRI: an assessment of six freely available software packages for cross-sectional analyses.

PURPOSE: Volume measurement using MRI is important to assess brain atrophy in multiple sclerosis (MS). However, differences between scanners, acquisition protocols, and analysis software introduce unwanted variability of volumes. To quantify theses effects, we compared within-scanner repeatability and between-scanner reproducibility of three different MR scanners for six brain segmentation methods. METHODS: Twenty-one people with MS underwent scanning and rescanning on three 3 T MR scanners (GE MR750, Philips Ingenuity, Toshiba Vantage Titan) to obtain 3D T1-weighted images. FreeSurfer, FSL, SAMSEG, FastSurfer, CAT-12, and SynthSeg were used to quantify brain, white matter and (deep) gray matter volumes both from lesion-filled and non-lesion-filled 3D T1-weighted images. We used intra-class correlation coefficient (ICC) to quantify agreement; repeated-measures ANOVA to analyze systematic differences; and variance component analysis to quantify the standard error of measurement (SEM) and smallest detectable change (SDC). RESULTS: For all six software, both between-scanner agreement (ICCs ranging 0.4-1) and within-scanner agreement (ICC range: 0.6-1) were typically good, and good to excellent (ICC > 0.7) for large structures. No clear differences were found between filled and non-filled images. However, gray and white matter volumes did differ systematically between scanners for all software (p < 0.05). Variance component analysis yielded within-scanner SDC ranging from 1.02% (SAMSEG, whole-brain) to 14.55% (FreeSurfer, CSF); and between-scanner SDC ranging from 4.83% (SynthSeg, thalamus) to 29.25% (CAT12, thalamus). CONCLUSION: Volume measurements of brain, GM and WM showed high repeatability, and high reproducibility despite substantial differences between scanners. Smallest detectable change was high, especially between different scanners, which hampers the clinical implementation of atrophy measurements.

ExploreASL: An image processing pipeline for multi-center ASL perfusion MRI studies.

Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.

Summarizing the 4D image stack of ultrafast dynamic contrast enhancement MRI of breast cancer in 3D using color intensity projections.

BACKGROUND: Each ultrafast dynamic contrast-enhanced (DCE) MRI sequence for breast cancer generates thousands of images in a 4D stack that need to be reviewed by a radiologist. PURPOSE: To assess whether color intensity projections (CIP) effectively summarizes-using only the time of arrival (ToA) and amount of signal enhancement (AoE) of the contrast agent-the thousands of ultrafast images. STUDY TYPE: Retrospective cohort clinical trial. SUBJECTS: The study included 89 patients who had been scanned with an MRI beast protocol, of which 26 had breast cancer and 63 did not. FIELD STRENGTH/SEQUENCE: The 115-second ultrafast DCE sequence at 3T acquired 19 consecutive frames every 4.26 seconds with 152 slices per frame, yielding a 4D stack with 2888 2D images for each of water and fat. ASSESSMENT: For each slice of the water 4D stack a single CIP image was generated that encoded the ToA in the hue (red, orange, yellow, green, cyan, blue) and AoE in the brightness. Each of three experienced radiologists assigned a Breast Imaging and Reporting Data System (BI-RADS) score for each patient, first using only the CIP images, and subsequently using both CIP and the full 4D stack. STATISTICAL TESTS: The one-sided Fisher's exact test was used to determine statistical significance of both the sensitivity and specificity between the CIP alone and the CIP plus 4D stack. RESULTS: All malignancies were detected using only CIP by at least one of the radiologists. The CIP and CIP+4D sensitivities for reader 1 were 96% and 96% (P = 0.57), specificities were 59% and 65% (P = 0.29). For reader 2, the values were 96% and 100% (P = 0.51) with 62% and 71% (P = 0.17). For reader 3 the values were 92% and 96% (P = 0.50) with 51% and 62% (P = 0.07). DATA CONCLUSION: With a 95% sensitivity, CIP provides an effective summary of ultrafast DCE images of breast cancer. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1391-1399.

Cerebral Microbleeds: Imaging and Clinical Significance.

Cerebral microbleeds (CMBs), also referred to as microhemorrhages, appear on magnetic resonance (MR) images as hypointense foci notably at T2*-weighted or susceptibility-weighted (SW) imaging. CMBs are detected with increasing frequency because of the more widespread use of high magnetic field strength and of newer dedicated MR imaging techniques such as three-dimensional gradient-echo T2*-weighted and SW imaging. The imaging appearance of CMBs is mainly because of changes in local magnetic susceptibility and reflects the pathologic iron accumulation, most often in perivascular macrophages, because of vasculopathy. CMBs are depicted with a true-positive rate of 48%-89% at 1.5 T or 3.0 T and T2*-weighted or SW imaging across a wide range of diseases. False-positive "mimics" of CMBs occur at a rate of 11%-24% and include microdissections, microaneurysms, and microcalcifications; the latter can be differentiated by using phase images. Compared with postmortem histopathologic analysis, at least half of CMBs are missed with premortem clinical MR imaging. In general, CMB detection rate increases with field strength, with the use of three-dimensional sequences, and with postprocessing methods that use local perturbations of the MR phase to enhance T2* contrast. Because of the more widespread availability of high-field-strength MR imaging systems and growing use of SW imaging, CMBs are increasingly recognized in normal aging, and are even more common in various disorders such as Alzheimer dementia, cerebral amyloid angiopathy, stroke, and trauma. Rare causes include endocarditis, cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy, and radiation therapy. The presence of CMBs in patients with stroke is increasingly recognized as a marker of worse outcome. Finally, guidelines for adjustment of anticoagulant therapy in patients with CMBs are under development. © RSNA, 2018.

Lower cerebral blood flow is associated with faster cognitive decline in Alzheimer's disease.

OBJECTIVE: To determine whether lower cerebral blood flow (CBF) is associated with faster cognitive decline in patients with Alzheimer's disease (AD). METHODS: We included 88 patients with dementia due to AD from the Amsterdam Dementia Cohort. Mean follow-up was 2 ± 1 years. Linear mixed models were used to determine associations of lower whole brain and regional pseudo-continuous arterial spin labelling measured CBF with rate of cognitive decline as measured with repeated mini-mental state examination (MMSE). Model 1 was adjusted for age, sex, and education. Model 2 was additionally adjusted for normalized gray matter volume, medial temporal lobe atrophy, white matter hyperintensities, microbleeds, and lacunes. Analyses were repeated after partial volume correction (PVC) of CBF. Statistical significance was set at p ≤ 0.05. RESULTS: Patients were 65 ± 7 years old, 44 (50 %) were women, and mean baseline MMSE was 22 ± 4. Annual decline (ß[SE]) on the MMSE was estimated at -2.11 (0.25) points per year. Lower whole brain (ß[SE]-0.50[0.25]; p ≤ 0.05) and parietal (ß[SE]-0.59[0.25]; p < 0.05) CBF were associated with faster cognitive decline. PVC cortical CBF was not associated with cognitive decline. CONCLUSIONS: Lower CBF, in particular in the posterior brain regions, may have value as a prognostic marker for rate of cognitive decline in AD. KEY POINTS: • In AD, lower CBF is associated with more rapid cognitive decline. • Decreasing CBF does not reach a plateau early in AD. • PcASL-CFB has additive value to conventional structural MRI measures in AD.

Strain analysis in CRT candidates using the novel segment length in cine (SLICE) post-processing technique on standard CMR cine images.

OBJECTIVES: Although myocardial strain analysis is a potential tool to improve patient selection for cardiac resynchronization therapy (CRT), there is currently no validated clinical approach to derive segmental strains. We evaluated the novel segment length in cine (SLICE) technique to derive segmental strains from standard cardiovascular MR (CMR) cine images in CRT candidates. METHODS: Twenty-seven patients with left bundle branch block underwent CMR examination including cine imaging and myocardial tagging (CMR-TAG). SLICE was performed by measuring segment length between anatomical landmarks throughout all phases on short-axis cines. This measure of frame-to-frame segment length change was compared to CMR-TAG circumferential strain measurements. Subsequently, conventional markers of CRT response were calculated. RESULTS: Segmental strains showed good to excellent agreement between SLICE and CMR-TAG (septum strain, intraclass correlation coefficient (ICC) 0.76; lateral wall strain, ICC 0.66). Conventional markers of CRT response also showed close agreement between both methods (ICC 0.61-0.78). Reproducibility of SLICE was excellent for intra-observer testing (all ICC ≥0.76) and good for interobserver testing (all ICC ≥0.61). CONCLUSIONS: The novel SLICE post-processing technique on standard CMR cine images offers both accurate and robust segmental strain measures compared to the 'gold standard' CMR-TAG technique, and has the advantage of being widely available. KEY POINTS: • Myocardial strain analysis could potentially improve patient selection for CRT. • Currently a well validated clinical approach to derive segmental strains is lacking. • The novel SLICE technique derives segmental strains from standard CMR cine images. • SLICE-derived strain markers of CRT response showed close agreement with CMR-TAG. • Future studies will focus on the prognostic value of SLICE in CRT candidates.

Increased cortical grey matter lesion detection in multiple sclerosis with 7 T MRI: a post-mortem verification study.

The relevance of cortical grey matter pathology in multiple sclerosis has become increasingly recognized over the past decade. Unfortunately, a large part of cortical lesions remain undetected on magnetic resonance imaging using standard field strength. In vivo studies have shown improved detection by using higher magnetic field strengths up to 7 T. So far, a systematic histopathological verification of ultra-high field magnetic resonance imaging pulse sequences has been lacking. The aim of this study was to determine the sensitivity of 7 T versus 3 T magnetic resonance imaging pulse sequences for the detection of cortical multiple sclerosis lesions by directly comparing them to histopathology. We obtained hemispheric coronally cut brain sections of 19 patients with multiple sclerosis and four control subjects after rapid autopsy and formalin fixation, and scanned them using 3 T and 7 T magnetic resonance imaging systems. Pulse sequences included T1-weighted, T2-weighted, fluid attenuated inversion recovery, double inversion recovery and T2*. Cortical lesions (type I-IV) were scored on all sequences by an experienced rater blinded to histopathology and clinical data. Staining was performed with antibodies against proteolipid protein and scored by a second reader blinded to magnetic resonance imaging and clinical data. Subsequently, magnetic resonance imaging images were matched to histopathology and sensitivity of pulse sequences was calculated. Additionally, a second unblinded (retrospective) scoring of magnetic resonance images was performed. Regardless of pulse sequence, 7 T magnetic resonance imaging detected more cortical lesions than 3 T. Fluid attenuated inversion recovery (7 T) detected 225% more cortical lesions than 3 T fluid attenuated inversion recovery (Z = 2.22, P < 0.05) and 7 T T2* detected 200% more cortical lesions than 3 T T2* (Z = 2.05, P < 0.05). Sensitivity of 7 T magnetic resonance imaging was influenced by cortical lesion type: 100% for type I (T2), 11% for type II (FLAIR/T2), 32% for type III (T2*), and 68% for type IV (T2). We conclude that ultra-high field 7 T magnetic resonance imaging more than doubles detection of cortical multiple sclerosis lesions, compared to 3 T magnetic resonance imaging. Unfortunately, (subpial) cortical pathology remains more extensive than 7 T magnetic resonance imaging can reveal.

Lower cerebral blood flow is associated with impairment in multiple cognitive domains in Alzheimer's disease.

INTRODUCTION: We examined the association between decreased cerebral blood flow (CBF) and cognitive impairment in Alzheimer's disease (AD), mild cognitive impairment (MCI), and subjective cognitive decline (SCD). METHODS: We included 161 AD, 95 MCI, and 143 SCD patients from the Amsterdam Dementia Cohort. We used 3-T pseudo-continuous arterial spin labeling to estimate whole-brain and regional partial volume-corrected CBF. Neuropsychological tests covered global cognition and five cognitive domains. Associations were investigated using linear regression analyses. RESULTS: In the whole sample, reduced overall and regional CBF was associated with impairment in all cognitive domains. We found significant interactions between diagnosis and CBF for language and between diagnosis and parietal CBF for global cognition and executive functioning. Stratification showed that decreased CBF was associated with worse performance in AD patients but not in MCI or SCD. DISCUSSION: Our results suggest that CBF may have potential as a functional marker of disease severity.

Application of Machine Learning to Arterial Spin Labeling in Mild Cognitive Impairment and Alzheimer Disease.

Purpose To investigate whether multivariate pattern recognition analysis of arterial spin labeling (ASL) perfusion maps can be used for classification and single-subject prediction of patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) and subjects with subjective cognitive decline (SCD) after using the W score method to remove confounding effects of sex and age. Materials and Methods Pseudocontinuous 3.0-T ASL images were acquired in 100 patients with probable AD; 60 patients with MCI, of whom 12 remained stable, 12 were converted to a diagnosis of AD, and 36 had no follow-up; 100 subjects with SCD; and 26 healthy control subjects. The AD, MCI, and SCD groups were divided into a sex- and age-matched training set (n = 130) and an independent prediction set (n = 130). Standardized perfusion scores adjusted for age and sex (W scores) were computed per voxel for each participant. Training of a support vector machine classifier was performed with diagnostic status and perfusion maps. Discrimination maps were extracted and used for single-subject classification in the prediction set. Prediction performance was assessed with receiver operating characteristic (ROC) analysis to generate an area under the ROC curve (AUC) and sensitivity and specificity distribution. Results Single-subject diagnosis in the prediction set by using the discrimination maps yielded excellent performance for AD versus SCD (AUC, 0.96; P < .01), good performance for AD versus MCI (AUC, 0.89; P < .01), and poor performance for MCI versus SCD (AUC, 0.63; P = .06). Application of the AD versus SCD discrimination map for prediction of MCI subgroups resulted in good performance for patients with MCI diagnosis converted to AD versus subjects with SCD (AUC, 0.84; P < .01) and fair performance for patients with MCI diagnosis converted to AD versus those with stable MCI (AUC, 0.71; P > .05). Conclusion With automated methods, age- and sex-adjusted ASL perfusion maps can be used to classify and predict diagnosis of AD, conversion of MCI to AD, stable MCI, and SCD with good to excellent accuracy and AUC values. © RSNA, 2016.

Cerebral perfusion in the predementia stages of Alzheimer's disease.

OBJECTIVES: To investigate arterial spin-labelling (ASL) cerebral blood flow (CBF) changes in predementia stages of Alzheimer's disease (AD). METHODS: Data were obtained from 177 patients with subjective complaints, mild cognitive impairment and AD from the Amsterdam Dementia Cohort. AD stages were based on diagnosis and cerebrospinal fluid biomarkers amyloid-ß (Aß) and total-tau (tau). General-linear-models were used to assess relationships between AD stages and total and regional CBF, correcting for age and sex. RESULTS: Decreasing CBF was related to more advanced AD stages in all supratentorial regions (p for trend < 0.05). Post-hoc testing revealed that CBF was lower in AD compared to controls and stage-1 predementia patients (i.e. abnormal Aß and normal tau) in temporal and parietal regions, and compared to stage-2 predementia patients (i.e. abnormal Aß and tau) in temporal regions. CBF values of stage-2 predementia patients were numerically in between those of stage-1 predementia patients and AD. CONCLUSION: The continuing decrease of CBF along the continuum of AD indicates the potential of ASL-CBF as a measure for disease progression. KEY POINTS: • Decreasing CBF relates to more advanced AD stages in all supratentorial regions. • The reduction of CBF does not reach a bottom level. • ASL-CBF has potential as a measure for disease progression in AD.

Cerebral perfusion and glucose metabolism in Alzheimer's disease and frontotemporal dementia: two sides of the same coin?

OBJECTIVES: Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [(18)F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD. METHODS: Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed. RESULTS: Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68). CONCLUSIONS: Similar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET. KEY POINTS: • Similar patterns of hypoperfusion and hypometabolism were observed in patients with dementia. • For both imaging modalities, parietal abnormalities were found in Alzheimer's disease. • For both imaging modalities, prefrontal abnormalities were found in frontotemporal dementia.

Reproducibility of pharmacological ASL using sequences from different vendors: implications for multicenter drug studies.

OBJECT: The current study assesses the multicenter feasibility of pharmacological arterial spin labeling (ASL) by comparing a caffeine-induced relative cerebral blood flow decrease (%CBF↓) measured with two pseudo-continuous ASL sequences as provided by two major vendors. MATERIALS AND METHODS: Twenty-two healthy volunteers were scanned twice with both a 3D spiral (GE) and a 2D EPI (Philips) sequence. The inter-session reproducibility was evaluated by comparisons of the mean and within-subject coefficient of variability (wsCV) of the %CBF↓, both for the total cerebral gray matter and on a voxel level. RESULTS: The %CBF↓ was larger when measured with the 3D spiral sequence (23.9 ± 5.9 %) than when measured with the 2D EPI sequence (19.2 ± 5.6 %) on a total gray matter level (p = 0.02), and on a voxel level in the posterior watershed area (p < 0.001). There was no difference between the gray matter wsCV of the 3D spiral (57.3 %) and 2D EPI sequence (66.7 %, p = 0.3), whereas on a voxel level, the wsCV was visibly different between the sequences. CONCLUSION: The observed differences between ASL sequences of both vendors can be explained by differences in the employed readout modules. These differences may seriously hamper multicenter pharmacological ASL, which strongly encourages standardization of ASL implementations.

MRI T2* mapping correlates with biochemistry and histology in intervertebral disc degeneration in a large animal model.

PURPOSE: To evaluate intervertebral disc (IVD) degeneration and treatments, an objective diagnostic tool is needed. Recently, T2* relaxation time mapping was proposed as a technique to assess early IVD degeneration, yet the correlation with biochemical content and histological features has not been investigated previously. Our objective was to validate T2* mapping for disc degeneration by correlating this technique with accepted parameters of IVD degeneration. METHODS: Mildly and severely degenerated lumbar discs were obtained from an in vivo large animal study; two healthy goat spines were acquired as control. In total, 48 IVDs were analysed using T2-weighted MRI, T2* relaxation time mapping, biochemical assays, macroscopic and histological scoring. Correlations between variables were expressed with Spearman's rho (ρ) coefficients. RESULTS: A complete range of degenerative grades were obtained (mean histological grade 2.2, range 0-6). A linear positive correlation was observed between T2* relaxation time and glycosaminoglycan content (ρ = 0.64, p < 0.001). T2* relaxation time decreased linearly with increasing degeneration as assessed with Pfirrmann scoring system (ρ = -0.67, p < 0.001), macroscopic (ρ = -0.33, p < 0.05) and histological (ρ = -0.45, p < 0.05) grading. CONCLUSIONS: T2* mapping is an MRI technique for IVD evaluation which allows for measurements on a continuous scale thus minimising observer bias compared to grading systems. Although limited by a small sample size, this study showed a relatively good and linear correlation between T2* relaxation time and accepted parameters of disc degeneration. This suggests that T2* mapping is a promising tool to assess disc degeneration in clinical practice.

Quantification of cerebral blood flow in healthy volunteers and type 1 diabetic patients: comparison of MRI arterial spin labeling and [(15)O]H2O positron emission tomography (PET).

PURPOSE: To compare cerebral blood flow (CBF) values measured using magnetic resonance imaging (MRI) arterial spin labeling (ASL) with those obtained with [(15)O]H2O positron emission tomography (PET), the gold standard for measuring CBF in vivo. MATERIALS AND METHODS: Data were collected in 11 healthy men and in 20 age- and body mass index (BMI)-matched type 1 diabetic men. Pseudo-continuous ASL (PCASL) data were acquired at 3 T and [(15)O]H2O PET scans were acquired using a high-resolution PET scanner. Input functions were obtained using on-line arterial blood sampling. Whole brain and regional CBF values were compared. RESULTS: For both modalities, whole brain CBF was similar in both subject groups. In groups combined, average whole brain CBF was 0.30 ± 0.05 mL · cm(-3) · min(-1) for [(15)O]H2O PET and 0.34 ± 0.05 mL · cm(-3) · min(-1) for ASL MRI (P < 0.01). A significant correlation between methods was observed for whole brain, gray and white matter. In 12 out of 33 brain regions a significant difference between methods was observed. CONCLUSION: PCASL provides CBF values that correlate with [(15)O]H2O PET-derived values, but is less accurate. PCASL may be an attractive alternative when absolute quantification is not needed.

Differentiation of edema and glioma infiltration: proposal of a DTI-based probability map.

Conflicting results on differentiating edema and glioma by diffusion tensor imaging (DTI) are possibly attributable to dissimilar spatial distribution of the lesions. Combining DTI-parameters and enhanced registration might improve prediction. Regions of edema surrounding 22 metastases were compared to tumor-infiltrated regions from WHO grade 2 (12), 3 (10) and 4 (18) gliomas. DTI data was co-registered using Tract Based Spatial Statistics (TBSS), to measure Fractional Anisotropy (FA) and Mean Diffusivity (MD) for white matter only, and relative changes compared to matching reference regions (dFA and dMD). A two-factor principal component analysis (PCA) on metastasis and grade 2 glioma was performed to explore a possible differentiating combined factor. Edema demonstrated equal MD and higher FA compared to grade 2 and 3 glioma (P < 0.001), but did not differ from glioblastoma. Differences were non-significant when corrected for spatial distribution, since reference regions differed strongly (P < 0.001). The second component of the PCA (PCA-C2) did differentiate edema and low-grade tumor (sensitivity 91.7%, specificity 86.4%). PCA-C2 scores were plotted voxel-wise as a probability-map, discerning distinct areas of presumed edema or tumor infiltration. Correction of spatial dependency appears essential when differentiating glioma from edema. A tumor-infiltration probability-map is presented, based on supplementary information of multiple DTI parameters and spatial normalization.

Improved differentiation between MS and vascular brain lesions using FLAIR* at 7 Tesla.

OBJECTIVES: To investigate whether a new magnetic resonance image (MRI) technique called T2*-weighted fluid attenuation inversion recovery (FLAIR*) can differentiate between multiple sclerosis (MS) and vascular brain lesions, at 7 Tesla (T). METHODS: We examined 16 MS patients and 16 age-matched patients with (risk factors for) vascular disease. 3D-FLAIR and T2*-weighted images were combined into FLAIR* images. Lesion type and intensity, perivascular orientation and presence of a hypointense rim were analysed. RESULTS: In total, 433 cerebral lesions were detected in MS patients versus 86 lesions in vascular patients. Lesions in MS patients were significantly more often orientated in a perivascular manner: 74 % vs. 47 % (P < 0.001). Ten MS lesions (2.3 %) were surrounded by a hypointense rim on FLAIR*, and 24 MS lesions (5.5 %) were hypointense on T2*. No lesions in vascular patients showed any rim or hypointensity. Specificity of differentiating MS from vascular lesions on 7-T FLAIR* increased when the presence of a central vessel was taken into account (from 63 % to 88 %), most obviously for deep white matter lesions (from 69 % to 94 %). High sensitivity remained (81 %). CONCLUSION: 7-T FLAIR* improves differentiation between MS and vascular lesions based on lesion location, perivascular orientation and presence of hypointense (rims around) lesions. KEY POINTS: • A new MRI technique T2*-weighted fluid attenuation inversion recovery (FLAIR*) was investigated. • FLAIR* at 7-T MRI combines FLAIR and T2* images into a single image. • FLAIR* at 7 T does not require enhancement with contrast agents. •High-resolution 7-T FLAIR* improves differentiation between MS and vascular brain lesions. • FLAIR* revealed a central vessel more frequently in MS than vascular lesions.

Distinct perfusion patterns in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies.

OBJECTIVES: To compare pseudo-continuous arterial spin-labelled (PCASL) magnetic resonance imaging (MRI) measured quantitative cerebral blood flow (CBF) of patients with frontotemporal dementia (FTD), dementia with Lewy Bodies (DLB), Alzheimer's disease (AD) and controls, in a region of interest (ROI) and voxel-wise fashion. METHODS: We analysed whole-brain 3D fast-spin-echo PCASL images of 20 FTD patients, 14 DLB patients, 48 AD patients and 50 controls from the Amsterdam Dementia Cohort. Regional CBF patterns were compared using analyses of variance for repeated measures. Permutation tests were used for voxel-wise comparisons. Analyses were performed using uncorrected and partial volume corrected (PVC) maps. All analyses were corrected for age and sex. RESULTS: There was an interaction between diagnosis and region (p < 0.001), implying differences in regional CBF changes between diagnostic groups. In AD patients, CBF was decreased in all supratentorial regions, most prominently so in the posterior regions. DLB patients showed lowest CBF values throughout the brain, but temporal CBF was preserved. Supratentorial PVC cortical CBF values were lowest in the frontal lobes in FTD patients, and in the temporal lobes in AD patients. CONCLUSIONS: Patients with AD, FTD and DLB display distinct patterns of quantitative regional CBF changes. 3D-PCASL may provide additional value in the workup of dementia patients. KEY POINTS: Patterns of regional CBF changes differ between AD, FTD and DLB patients. CBF is lower throughout the brain in DLB than AD and FTD. 3D-PCASL MRI is a potential non-invasive and easily accessible alternative to FDG-PET. 3D-PCASL MRI may be of additional value in the workup of dementia.

MRI in patients with a cerebral aneurysm clip; review of the literature and incident databases and recommendations for the Netherlands.

BACKGROUND: In the past ferromagnetic cerebral aneurysm clips that are contraindicated for Magnetic Resonance Imaging (MRI) have been implanted. However, the specific clip model is often unknown for older clips, which poses a problem for individual patient management in clinical care. METHODS: Literature and incident databases were searched, and a survey was performed in the Netherlands that identified time periods at which ferromagnetic and non-ferromagnetic clip models were implanted. Considering this information in combination with a national expert opinion, we describe an approach for risk assessment prior to MRI examinations in patients with aneurysm clips. The manuscript is limited to MRI at 1.5 T or 3 T whole body MRI systems with a horizontal closed bore superconducting magnet, covering the majority of clinical Magnetic Resonance (MR) systems. RESULTS: From the literature a list of ferromagnetic clip models was obtained. The risk of movement or rotation of the clip due to the main magnetic field in case of a ferromagnetic clip is the main concern. In the incident databases records of four serious incidents due to aneurysm clips in MRI were found. The survey in the Netherlands showed that from 2000 onwards, no ferromagnetic clips were implanted in Dutch hospitals. DISCUSSION: Recommendations are provided to help the MR safety expert assessing the risks when a patient with a cerebral aneurysm clip is referred for MRI, both for known and unknown clip models. This work was part of the development of a guideline by the Dutch Association of Medical Specialists.

Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer's disease (DEBBIE-AD): a prospective observational multicohort study protocol.

INTRODUCTION: Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer's disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). METHODS AND ANALYSIS: DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies. ETHICS AND DISSEMINATION: Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.