Comparison of pulsed arterial spin labeling encoding schemes and absolute perfusion quantification

Arterial spin labeling (ASL) using magnetic resonance imaging (MRI) is a powerful noninvasive technique to investigate the physiological status of brain tissue by measuring cerebral blood flow (CBF). ASL assesses the inflow of magnetically labeled arterial blood into an imaging voxel. In the last 2 decades, various ASL sequences have been proposed which differ in their ease of implementation and their sensitivity to artifacts. In addition, several quantification methods have been developed to determine the absolute value of CBF from ASL magnetization difference images. In this study, we evaluated three pulsed ASL sequences and three absolute quantification schemes. It was found that FAIR-QUIPSSII implementation of ASL yields 10–20% higher signal-to-noise ratio (SNR) and 18% higher CBF as compared with PICORE-Q2TIPS (with FOCI pulses) and PICORE-QUIPSSII (with BASSI pulses). In addition, quantification schemes employed can give rise to up to a 35% difference in CBF values. We conclude that, although all quantitative ASL sequences and CBF calibration methods should in principle result in the similar CBF values and image quality, substantial differences in CBF values and SNR were found. Thus, comparing studies using different ASL sequences and analysis algorithms is likely to result in erroneous intra- and intergroup differences. Therefore, (i) the same quantification schemes should consistently be used, and (ii) quantification using local tissue proton density should yield the most accurate CBF values because, although still requiring definitive demonstration in future studies, the proton density of blood is assumed to be very similar to the value of gray matter.     

Improving cerebral blood flow quantification for arterial spin labeled perfusion MRI by removing residual motion artifacts and global signal fluctuations

Denoising is critical to improving the quality and stability of cerebral blood flow (CBF) quantification in arterial spin labeled (ASL) perfusion magnetic resonance imaging (MRI) due to the intrinsic low signal-to-noise-ratio (SNR) of ASL data. Previous studies have been focused on reducing the spatial or temporal noise using standard filtering techniques, and less attention has been paid to two global nuisance effects, the residual motion artifacts and the global signal fluctuations. Since both nuisances affect the whole brain, removing them in advance should enhance the CBF quantification quality for ASL MRI. The purpose of this paper was to assess this potential benefit. Three methods were proposed to suppress each or both of the two global nuisances. Their performances for CBF quantification were validated using ASL data acquired from 13 subjects. Evaluation results showed that covarying out both global nuisances significantly improved temporal SNR and test-retest stability of CBF measurement. Although the concept of removing both nuisances is not technically novel per se, this paper clearly showed the benefits for ASL CBF quantification. Dissemination of the proposed methods in a free ASL data processing toolbox should be of interest to a broad range of ASL users.     

Evaluation of B0-correction of relative CBF maps using tagging distance dependent Z-spectrum (TADDZ)

Arterial spin labeling (ASL) MRI, based on endogenous contrast from blood water, is used in research and diagnosis of cerebral vascular conditions. However, artifacts due to imperfect imaging conditions such as B₀-inhomogeneity (ΔB₀) could lead to variations in the quantification of relative cerebral blood flow (CBF). In this study, we evaluate a new approach using tagging distance dependent Z-spectrum (TADDZ) data, similar to the ΔB₀ corrections in the chemical exchange saturation transfer (CEST) experiments, to remove the imaging plane B₀ inhomogeneity induced CBF artifacts in ASL MRI. Our results indicate that imaging-plane B₀-inhomogeneity can lead to variations and errors in the relative CBF maps especially under small tagging distances. Along with an acquired B₀ map, TADDZ data helps to eliminate B₀-inhomogeneity induced artifacts in the resulting relative CBF maps. We demonstrated the effective use of TADDZ data to reduce variation while subjected to systematic changes in ΔB₀. In addition, TADDZ corrected ASL MRI, with improved consistency, was shown to outperform conventional ASL MRI by differentiating the subtle CBF difference in Alzheimer's disease (AD) mice brains with different APOE genotypes.     

In vivo measurement of tissue damage, oxygen saturation changes and blood flow changes after experimental traumatic brain injury in rats using susceptibility weighted imaging

Traumatic brain injury (TBI) is a prevalent disease, and many TBI patients experience disturbed cerebral blood flow (CBF) after injury. Moreover, TBI is difficult to quantify with conventional imaging modalities. In this paper, we utilized susceptibility weighted imaging (SWI) as a means to monitor functional blood oxygenation changes and to quantify CBF changes in animals after trauma. In this study using six rats, brain trauma was induced by a weight drop model and the brain was scanned over four time points: pre trauma, and 4 h, 24 h and 48 h post trauma. Five rats survived and one died after trauma. A blood phase analysis using filtered SWI phase images suggested that three rats recovered after 48 h and two rats deteriorated. SWI also suggested that CBF decreased by up to 26%. The CBF change is in agreement with the results of arterial spin labeling methods conducted in this study and with previously published results. Furthermore, SWI revealed an enlargement of the major venous vasculature in deep brain structures, in accordance with the location of diffuse axonal injury. Compared with the traditional, invasive, clinical monitoring of cerebral vascular damage and reduction in blood flow, this method offers a novel, safe and noninvasive approach to quantify changes in oxygen saturation and CBF and to visualize structural changes in blood vasculature after TBI.     

Absolute quantification of cerebral blood flow: correlation between dynamic susceptibility contrast MRI and model-free arterial spin labeling

Purpose

To compare absolute cerebral blood flow (CBF) estimates obtained by model-free arterial spin labeling (ASL) and dynamic susceptibility contrast MRI (DSC-MRI), corrected for partial volume effects (PVEs).

Methods

CBF was measured using DSC-MRI and model-free ASL (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) at 3 T in 15 subjects with brain tumor, and the two modalities were compared with regard to CBF estimates in normal gray matter (GM) and DSC-to-ASL CBF ratios in selected tumor regions. The DSC-MRI CBF maps were calculated using a global arterial input function (AIF) from the sylvian-fissure region, but, in order to minimize PVEs, the AIF time integral was rescaled by a venous output function time integral obtained from the sagittal sinus.

Results

In GM, the average DSC-MRI CBF estimate was 150±45 ml/(min 100 g) (mean±SD) while the corresponding ASL CBF was 44±10 ml/(min 100 g). The linear correlation between GM CBF estimates obtained by DSC-MRI and ASL was r=.89, and observed DSC-to-ASL CBF ratios differed by less than 3% between GM and tumor regions.

Conclusions

A satisfactory positive linear correlation between the CBF estimates obtained by model-free ASL and DSC-MRI was observed, and DSC-to-ASL CBF ratios showed no obvious tissue dependence.     

Quantification of cerebral blood flow in nonhuman primates using arterial spin labeling and a two-compartment model

Noninvasive absolute quantification of cerebral blood flow (CBF) with high spatial resolution is still a challenging task. Arterial spin labeling (ASL) is a promising magnetic resonance imaging (MRI) method for accurate perfusion quantification. However, modeling of ASL data is far from being standardized and has not been investigated in great detail. In this study, two-compartment modeling of monkey ASL data in three physiological conditions (baseline, sensory activated and globally elevated CBF) is reported. Absolute perfusion and arterial transit times were derived for gray matter (GM) and white matter (WM) separately. The uncertainties of the model's result were determined by Monte Carlo simulations. The fitted CBF values for GM were 133 ml/min/100 ml at baseline condition, 165 ml/min/100 ml during visual stimulation and 234 ml/min/100 ml for globally elevated CBF after intravenous injection of acetazolamide. The ratio of GM to WM CBF was 2.5 at baseline and was found to decrease to 1.6 after application of acetazolamide. The corresponding arterial transit times decreased from 742 to 607 ms in GM and from 985 to 875 ms in WM. Monte Carlo simulations showed that absolute CBF values can be determined with an error of 11-15%, while the arterial transit time values have a coefficient of variation of 25-31%. With an alternative acquisition scheme, the precision of the arterial transit times can be improved significantly. The CBF values in the occipital lobe of the monkey brain quantified with ASL are higher than previously reported in positron emission tomography studies.     

Denoising arterial spin labeling perfusion MRI with deep machine learning

PurposeArterial spin labeling (ASL) perfusion MRI is a noninvasive technique for measuring cerebral blood flow (CBF) in a quantitative manner. A technical challenge in ASL MRI is data processing because of the inherently low signal-to-noise-ratio (SNR). Deep learning (DL) is an emerging machine learning technique that can learn a nonlinear transform from acquired data without using any explicit hypothesis. Such a high flexibility may be particularly beneficial for ASL denoising. In this paper, we proposed and validated a DL-based ASL MRI denoising algorithm (DL-ASL).MethodsThe DL-ASL network was constructed using convolutional neural networks (CNNs) with dilated convolution and wide activation residual blocks to explicitly take the inter-voxel correlations into account, and preserve spatial resolution of input image during model learning.ResultsDL-ASL substantially improved the quality of ASL CBF in terms of SNR. Based on retrospective analyses, DL-ASL showed a high potential of reducing 75% of the original acquisition time without sacrificing CBF measurement quality.ConclusionDL-ASL achieved improved denoising performance for ASL MRI as compared with current routine methods in terms of higher PSNR, SSIM and Radiologic scores. With the help of DL-ASL, much fewer repetitions may be prescribed in ASL MRI, resulting in a great reduction of the total acquisition time.     

Intracranial vascular feature changes in time of flight MR angiography in patients undergoing carotid revascularization surgery

PurposeTo characterize the intracranial vascular features extracted from time of flight (TOF) images and their changes from baseline to follow-up in patients undergoing carotid revascularization, using arterial spin labeling (ASL) cerebral blood flow (CBF) measurement as a reference.MethodsIn this retrospective study, brain TOF and ASL images of 99 subjects, acquired before, within 48 h, and/or 6 months after, carotid revascularization surgery were analyzed. TOF images were analyzed using a custom software (iCafe) to quantify intracranial vascular features, including total vessel length, total vessel volume, and number of branches. Mean whole-brain CBF was calculated from ASL images. ASL scans showing low ASL signal in the entire flow territory of an internal carotid artery (ICA), which may be caused by labeling failure, were excluded. Changes and correlations between time points were analyzed separately for TOF intracranial vascular features and ASL CBF.ResultsSimilar to ASL CBF, TOF vascular features (i.e. total vessel length, total vessel volume and number of branches) increased dramatically from baseline to post-surgery, then returned to a level slightly higher than the baseline in long-term follow-up (All P < 0.05). Correlation between time points was observed for all three TOF vascular features but not for ASL CBF.ConclusionIntracranial vascular features, including total vessel length, total vessel volume and number of branches, extracted from TOF images are useful in detecting brain blood flow changes induced by carotid revascularization surgery.     

Reliability and reproducibility of perfusion MRI in cognitively normal subjects

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is becoming a popular method for measuring perfusion due to its ability of generating perfusion maps noninvasively. This allows for frequent repeat scanning, which is especially useful for follow-up studies. However, limited information is available regarding the reliability and reproducibility of ASL perfusion measurements. Here, the reliability and reproducibility of pulsed ASL was investigated in an elderly population to determine the variation in perfusion among cognitively normal individuals in different brain structures. Intraclass correlation coefficients (ICC) and within-subject variation coefficients (wsCV) were used to estimate reliability and reproducibility over a period of 1 year. Twelve cognitively normal subjects (75.5±5.3 years old, six male and six female) were scanned four times (at 0, 3, 6 and 12 months). No significant difference in cerebral blood flow (CBF) was found over this period. CBF values ranged from 46 to 53 ml/100 g per minute in the medial frontal gyrus (MFG) and from 40 to 44 ml/100 g per minute over all gray matter regions in the superior part of the brain. Data obtained from the first two scans were processed by two readers and showed high reliability (ICC >0.97) and reproducibility (wsCV <6%). However, over the total period of 1 year, reliability reduced to a moderate level (ICC=0.63–0.74) with wsCVs of gray matter, left MFG, right MFG of 13.5%, 12.3%, and 15.4%, respectively. In conclusion, measurement of CBF with pulsed ASL provided good agreement between inter-raters. A moderate level of reliability was obtained over a 1-year period, which was attributed to variance in slice positioning and coregistration. As such pulsed ASL has the potential to be used for CBF comparison in longitudinal studies.     

Robust estimation of the cerebral blood flow in arterial spin labelling

The introduction of arterial spin labelling (ASL) techniques in magnetic resonance imaging (MRI) has made feasible a non-invasive measurement of the cerebral blood flow (CBF). However, to date, the low signal-to-noise ratio of ASL gives us no option but to repeat the acquisition to accumulate enough data in order to get a reliable signal. The perfusion signal is then usually extracted by averaging across the repetitions. But the sample mean is very sensitive to outliers. A single incorrect observation can therefore be the source of strong detrimental effects on the perfusion-weighted image estimated with the sample mean.     

A comparison study between the saturation-recovery-T1 and CASL MRI methods for quantitative CBF imaging

The saturation-recovery (SR)-T₁ MRI method for quantitatively imaging cerebral blood flow (CBF) change (ΔCBF) concurrently with the blood oxygenation level dependence (BOLD) alteration has been recently developed and validated by simultaneous measurement of relative CBF change using laser Doppler flowmetry (LDF) in rats at 9.4T. In this study, ΔCBF induced by mildly transient hypercapnia and measured by the SR-T₁ MRI method was rigorously compared with an established perfusion MRI method—continuous arterial spin labeling (CASL) approach in normal and preclinical middle cerebral artery occlusion (MCAo) rat models. The results show an excellent agreement between ΔCBF values measured with these two imaging methods. Moreover, the intrinsic longitudinal relaxation rate (R₁^int) was experimentally determined in vivo in normal rat brains at 9.4T by comparing two independent measures of the apparent longitudinal relaxation rate (R₁^app) and CBF measured by the CSAL approach across a wide range of perfusion. In turn, the R₁^int constant can be employed to calculate the CBF value based on the R₁^app measurement in healthy brain. This comparison study validates the fundamental relationship for linking brain tissue water R₁^app and cerebral perfusion, demonstrates the feasibility of imaging and quantifying both CBF and its change using the SR-T₁ MRI method in vivo.     

On the sensitivity of ASL MRI in detecting regional differences in cerebral blood flow

Arterial-spin-labeling (ASL) magnetic resonance imaging (MRI) provides a noninvasive tool to measure cerebral blood flow (CBF) and is increasingly used as a surrogate for baseline neural activity. However, the power of ASL MRI in detecting CBF differences between patient and control subjects is hampered by inter-subject variations in global CBF, which are associated with non-neural factors and may contribute to the noise in the across-group comparison. Here, we investigated the sensitivity of this technique and proposed a normalization strategy to better detect such a difference. A “model” situation was employed in which two visual stimuli (i.e. cross fixation and flashing checkerboard) were presented to two groups of subjects to mimic “control” and “patient” groups (N=7 for each group), respectively. It was found that absolute CBF (aCBF) in the occipital lobe in the checkerboard group was 26.0% greater compared to the fixation group, but the level of significance was modest (P=.03). In contrast, when normalizing the CBF with whole-brain CBF or CBF in a reference region [termed relative CBF (rCBF)], the statistical significance was improved considerably (P<.003). For voxel-based analysis, the rCBF indices correctly detected CBF differences in the occipital lobe in the across-group comparison, while aCBF failed to detect any significant cluster using the same statistical threshold. We also performed Monte Carlo simulation to confirm the experimental findings and found that the power improvement was most pronounced when signal-to-noise-ratio is moderate and the underlying CBF difference was small. The simulation also showed that, with the proposed normalization, a detection power of 80% can be achieved using a sample size of about 20. In summary, rCBF is a more sensitive index to detect small differences in CBF, rather than the much-sought-after aCBF, since it reduces data noise caused by inter-subject variations in global CBF.     

Susceptibility weighted imaging in detecting hemorrhage in acute cervical spinal cord injury

Background and Purpose

Susceptibility weighted imaging (SWI) is sensitive to deoxyhemoglobin and blood products such as hemosiderin in detecting microbleeds in the brain. However, there are no studies on SWI in the spine cord injury so far. The purpose of this study was to evaluate the role of SWI in detecting hemorrhage in acute cervical spinal cord injury (SCI).

Materials and Methods

Twenty-three patients with a history of acute cervical spine trauma were studied. High-resolution SWI, gradient-echo (GRE) T2* weighted-image (T2*WI) and conventional magnetic resonance imaging (MRI) were performed on all patients within 15 days of the onset of injury. On the basis of the MRI findings, the patients were classified into four patterns: normal cord, spinal cord edema, spinal cord contusion and spinal cord hemorrhage. Quantitative analysis was performed by calculating and comparing the signal ratio of the hemorrhage to normal spinal cord on the same slice of T2*WI and SWI. All patients were clinically evaluated in follow-up. Twenty volunteers were also scanned as a control group.

Results

Out of 23 patients with a history of acute cervical spine trauma, 4 patients showed normal spinal cord on both conventional MRI and SWI, 8 had only spinal cord edema and 5 had contusion on conventional MRI, but SWI showed hemorrhage in 2 of the 5 patients with spinal contusion on conventional MRI; the other 6 patients had intraspinal hemorrhage on conventional MRI, and SWI proved hemorrhage in all these 6 patients. There was a significant difference between the signal ratios of hemorrhage to normal tissue on T2*WI and SWI (Z=2.34, P=.02).

Conclusion

Susceptibility weighted imaging is more sensitive than conventional MRI in detecting hemorrhage in acute cervical SCI. This technique could prove to be a useful tool in the routine evaluation of cervical SCI patients.     

Validation study of a pulsed arterial spin labeling technique by comparison to perfusion computed tomography

Abnormalities in cerebral blood flow (CBF) are believed to play a significant role in the development of major neonatal neuropathologies. One approach that would appear ideal for measuring CBF in this fragile age group is arterial spin labeling (ASL) since ASL techniques are noninvasive and quantitative. The purpose of this study was to assess the accuracy of a pulsed ASL method implemented on a 3-T scanner dedicated to neonatal imaging. Cerebral blood flow was measured in nine neonatal piglets, the ASL–CBF measurements were acquired at two inversion times (TI) (1200 and 1700 ms), and CBF was measured by perfusion computed tomography (pCT) for validation. Perfusion CT also provided images of cerebral blood volume, which were used to identify large blood vessels, and contrast arrival time, which were used to assess differences in arterial transit times between gray and white matter. Good agreement was found between gray matter CBF values from pCT (76±1 ml/min per 100 g) and ASL at TI=1700 ms (73±1 ml/min per 100 g). At TI=1200 ms, ASL overestimated CBF (91±2 ml/min per 100 g), which was attributed to substantial intravascular signal. No significant differences in white matter CBF from pCT and ASL were observed (average CBF=60±1 ml/min per 100 g), nor was there any difference in contrast arrival times for gray and white matter (0.95±0.04 and 0.99±0.03 s, respectively), which suggests that the arterial transit times for ASL were the same in this animal model. This study verified the accuracy of the implemented ASL technique and showed the value of using pCT to study other factors that can affect ASL–CBF measurements.     

Abnormalities of cerebral blood flow in multiple sclerosis: A pseudocontinuous arterial spin labeling MRI study

Arterial spin labeling (ASL) is a noninvasive technique that can measure cerebral blood flow (CBF). To our knowledge, there is no study that examined regional CBF of multiple sclerosis (MS) patients by using this technique. The present study assessed the relationship between clinical presentations and functional imaging data in MS using pseudocontinuous arterial spin labeling (pCASL). Twenty-seven patients with MS and 24 healthy volunteers underwent magnetic resonance imaging and pCASL to assess CBF. Differences in CBF between the two groups and the relationships of CBF values with the T2-hyperintense volume were evaluated. Compared to the healthy volunteers, reduced CBF was found in the bilateral thalami and right frontal region of the MS patients. The volume of the T2-hyperintense lesion was negatively correlated with regional CBF in some areas, such as both thalami. Our results suggest that demyelinated lesions in MS mainly have a remote effect on the thalamus and that the measurement of CBF using ASL could be an objective marker for monitoring disease activity in MS.     

Test-retest reliability and reproducibility of long-label pseudo-continuous arterial spin labeling

PurposeArterial spin labeling MRI can quantify the cerebral blood flow (CBF) without exogenous tracer. However, the variation of arterial transit time across different brain regions introduces bias for measuring local CBF, especially for those subjects with long arterial transit time (ATT). Long post-labeling delay (PLD) or multi-PLD methods could mitigate the problem of heterogenous ATT at the expense of the signal-to-noise ratio (SNR). Long-label ASL might address the low SNR problem by increasing the amount of labeled arterial blood. Thus, we hypothesized that with the same relatively long PLD, long-label pCASL may be more robust and reproducible than standard-label pCASL in population with potentially prolonged ATT. The purpose of the study was to investigate the reliability and reproducibility of long-label pCASL in the whole brain and vascular regions of interest in an elderly population, compared with standard-label pCASL.MethodTwenty adult volunteers (14 males, 6 females; age, 56.6 ± 17.2 years) were scanned twice on one 3.0 T scanner by standard-label pCASL (label duration (LD) = 1500 ms, PLD = 2000 ms) and long-label pCASL (LD = 3500 ms, PLD = 2000 ms). The intraclass correlation coefficient (ICC), within-subject coefficient of variation (wsCV), random noise and signal coefficient of variation(CoV) were used to assess global and regional reliability and reproducibility. Measurement agreement and difference were compared in different brain regions using correlation coefficient plots and Bland-Altman plots respectively.ResultsCBF value measured by long-label pCASL was overall higher than standard-label pCASL in all ROIs. Long-label pCASL had higher ICC than standard-label pCASL in most ROIs, and lower wsCV, random noise and CoV in all ROIs. Regardless of ASL method used, anterior circulation flow territories (ICC, 0.93–0.97; wsCV, 0.03–0.06) had higher CBF reliability and reproducibility than posterior circulation flow territories (ICC, 0.89; wsCV, 0.06–0.08). In all ROIs, the correlation analysis showed higher test-retest agreement (r_long-label > r_{standard-label}) and the Bland-Altman plots demonstrated lower measurement difference in long-label pCASL.ConclusionThe study demonstrated good reliability and reproducibility of long-label pCASL in anterior brain regions in the elderly population. To further improve CBF quantification in a long-ATT population while proper PLD is already used, increasing the label duration may help.     

Quantification of cerebral blood flow by bolus tracking and artery spin tagging methods

This study deals with perfusion quantification in healthy volunteers using two types of dynamic magnetic resonance imaging (MRI) methods. Absolute cerebral blood flow (CBF) measurements were performed in 11 subjects by applying both bolus tracking of exogenous contrast agent and non-invasive arterial spin labeling MRI techniques. Both methods produced CBF images with good tissue contrast and CBF values are in good agreement with literature data. The correlation between cerebral blood volume (CBV) and CBF is also discussed.     

An investigation of the relationship between BOLD and perfusion signal changes during epileptic generalised spike wave activity

In pathological conditions interpretation of functional magnetic resonance imaging (fMRI) results can be difficult. This is due to a reliance on the assumed coupling between neuronal activity and changes in cerebral blood flow (CBF) and oxygenation. We wanted to investigate the coupling between blood oxygen level dependant contrast (BOLD) and CBF time courses in epilepsy patients with generalised spike wave activity (GSW) to better understand the underlying mechanisms behind the EEG-fMRI signal changes observed, especially in regions of negative BOLD response (NBR). Four patients with frequent GSW were scanned with simultaneous electroencephalographic (EEG)-fMRI with BOLD and arterial spin labeling (ASL) sequences. We examined the relationship between simultaneous CBF and BOLD measurements by looking at the correlation of the two signals in terms of percentage signal change on a voxel-by-voxel basis. This method is not reliant on coincident activation. BOLD and CBF were positively correlated in patients with epilepsy during background EEG activity and GSW. The subject average value of the Delta CBF/Delta BOLD slope lay between +19 and +36 and also showed spatial variation which could indicate areas with altered vascular response. There was not a significant difference between Delta CBF/Delta BOLD during GSW, suggesting that neurovascular coupling to BOLD signal is generally maintained between states and, in particular, within areas of NBR.     

Atlas-based and DTI-guided quantification of human brain cerebral blood flow: Feasibility,quality assurance,spatial heterogeneity and age effects

Accurate and noninvasive quantification of regional cerebral blood perfusion (CBF) of the human brain tissue would advance the study of the complex interplay between human brain structure and function, in both health and disease. Despite the plethora of works on CBF in gray matter, a detailed quantitative white matter perfusion atlas has not been presented on healthy adults using the International Consortium for Brain Mapping atlases. In this study, we present a host of assurance measures such as temporal stability, spatial heterogeneity and age effects of regional and global CBF in selected deep, cortical gray matter and white matter tracts identified and quantified using diffusion tensor imaging (DTI). We utilized whole brain high-resolution DTI combined with arterial spin labeling to quantify regional CBF on 15 healthy adults aged 23.2–57.1 years. We present total brain and regional CBF, corresponding volume, mean diffusivity and fractional anisotropy spatial heterogeneity, and dependence on age as additional quality assurance measures to compare with published trends using both MRI and nuclear medicine methods. Total CBF showed a steady decrease with age in gray matter (r=?0.58; P= .03), whereas total CBF of white matter did not significantly change with age (r= 0.11; P= .7). This quantitative report offers a preliminary baseline of CBF, volume and DTI measurements for the design of future multicenter and clinical studies utilizing noninvasive perfusion and DT-MRI.     

Longitudinal brain imaging of five malignant glioma patients treated with bevacizumab using susceptibility-weighted magnetic resonance imaging at 7 T

Malignant glioma is a rare tumor type characterized by prominent vascular proliferation. Antiangiogenic therapy with the monoclonal antibody bevacizumab is considered as a promising therapeutic strategy, although the effect on tumor vascularization is unclear. High-field susceptibility-weighted imaging (SWI) visualizes the microvasculature and may contribute to the investigation of antiangiogenic therapy responses in gliomas. We prospectively studied five adult malignant glioma patients treated with bevacizumab-containing regimens. In each patient, we performed three 7-T SWI and T1-weighted imaging investigations (baseline and 2 and 4 weeks after the start of bevacizumab treatment). In addition, we imaged a postmortem brain of a patient with glioblastoma using 7-T SWI and performed detailed histopathological analysis. We observed almost total resolution of brain edema in three of five patients after initiation of bevacizumab therapy. In one case with rapid increase of the lesion size despite bevacizumab therapy, SWI showed progressive increase of irregular hypointense structures, most likely corresponding to increasing amounts of pathological microvasculature. In one case with progressive neurological decline, 7-T images showed multiple intratumoral microhemorrhages after the first bevacizumab application. Correlation of postmortem neuroimaging with histopathology confirmed that SWI-positive structures correspond to tumor vasculature. The experience from our case series indicates that longitudinal 7-T SWI seems to be an appropriate method for investigation of changes in brain tumor vascularization over time under antiangiogenic therapy.