Blood‐oxygen level dependent MRI measures of cerebrovascular reactivity using a controlled respiratory challenge: Reproducibility and gender differences

Purpose:

To evaluate the reproducibility and gender differences in cerebrovascular reactivity (CVR) measurements obtained using the blood‐oxygen level dependent (BOLD) response to controlled changes in end‐tidal partial pressure of carbon dioxide (PET CO₂).

Materials and Methods:

We obtained ethical approval to image 19 healthy volunteers (10 men, 9 women) on a 1.5 Tesla (T) MRI scanner twice on two separate days using identical procedures. CVR images were generated by collecting BOLD MRI data during controlled changes in PET CO₂ induced by a sequential gas delivery system.

Results:

Using the intraclass correlation coefficient (ICC), we demonstrated excellent within‐day CVR measures in gray matter (GM) (ICC = 0.92) and white matter (WM) (ICC = 0.88) regions, excellent between‐day reproducibility in GM (ICC = 0.81), and good between‐day reproducibility in the WM (ICC = 0.66). CVR values between men and women were significantly different in the GM and WM. Men exhibited a 22 ± 2% greater CVR in GM and a 17 ± 2% greater CVR in WM compared with females.

Conclusion:

Our results demonstrate the reliability of BOLD MRI CVR measurements obtained using a controlled cerebrovascular challenge. Using this technique, we also revealed significantly increased BOLD response to CO₂ in males compared with females. J. Magn. Reson. Imaging 2010; 31: 298–304. © 2010 Wiley‐Liss, Inc.     

Comparison of pulsed and pseudocontinuous arterial spin-labeling for measuring CO2 -induced cerebrovascular reactivity

Purpose:

To compare the performance of pulsed and pseudocontinuous arterial spin‐labeling (PASL and pCASL) methods in measuring CO₂‐induced cerebrovascular reactivity (CVR).

Materials and Methods:

Subjects were scanned using both ASL sequences during a controlled hypercapnia procedure and visual stimulation. CVR was computed as the percent CO₂‐induced increase in cerebral blood flow (Δ%CBF) per mmHg increase in end‐tidal PCO₂. Visually evoked responses were expressed as Δ%CBF. Resting CBF and temporal signal‐to‐noise ratio were also computed. Regionally averaged values for the different quantities were compared in gray matter (GM) and visual cortex (VC) using t‐tests.

Results:

Both PASL and pCASL yielded comparable respective values for resting CBF (56 ± 3 and 56 ± 4 mL/min/100g) and visually evoked responses (75 ± 5% and 81 ± 4%). Values of CVR determined using pCASL (GM 4.4 ± 0.2, VC 8 ± 1 Δ%CBF/mmHg), however, were significantly higher than those measured using PASL (GM 3.0 ± 0.6, VC 5 ± 1 Δ%CBF/mmHg) in both GM and VC. The percentage of GM voxels in which statistically significant hypercapnia responses were detected was also higher for pCASL (27 ± 5% vs. 16 ± 3% for PASL).

Conclusion:

pCASL may be less prone to underestimation of CO₂‐induced flow changes due to improved label timing control. J. Magn. Reson. Imaging 2012;36:312–321. © 2012 Wiley Periodicals, Inc.     

Feasibility and precision of cerebral blood flow and cerebrovascular reactivity MRI measurements using a computer-controlled gas delivery system in an anesthetised juvenile animal model

Purpose:

To demonstrate the feasibility and repeatability of cerebrovascular reactivity (CVR) imaging using a controlled CO₂ challenge in mechanically ventilated juvenile pigs.

Materials and Methods:

Precise end‐tidal partial pressure CO₂ (PETCO ₂) control was achieved via a computer‐controlled model‐driven prospective end‐tidal targeting (MPET) system integrated with mechanical ventilation using a custom‐built secondary breathing circuit. Test‐retest blood‐oxygen level dependent (BOLD) CVR images were collected in nine juvenile pigs by quantifying the BOLD response to iso‐oxic square‐wave PET CO₂ changes. For comparison, test‐retest baseline arterial spin labeling (ASL) cerebral blood flow (CBF) images were collected. Repeatability was quantified using the intra‐class correlation coefficient (ICC) and coefficient of variation (CV).

Results:

The repeatability of the PETCO₂ (CV < 2%) step changes resulted in BOLD CVR ICC > 0.94 and CV < 6% for cortical brain regions, which was similar to ASL CBF repeatability (ICC > 0.96 and CV < 4%).

Conclusion:

This study demonstrates the feasibility and precision of CVR imaging with an MPET CO₂ challenge in mechanically ventilated subjects using an animal model. Translation of this method into clinical imaging protocols may enable CVR imaging in young children with cerebrovascular disease who require general anesthesia. J. Magn. Reson. Imaging 2010;32:1068–1075. © 2010 Wiley‐Liss, Inc.     

Feasibility study of exploring a T₁-weighted dynamic contrast-enhanced MR approach for brain perfusion imaging

Purpose:

To investigate the feasibility of T₁‐weighted dynamic contrast‐enhanced (DCE) MRI for the measurement of brain perfusion.

Materials and Methods:

Dynamic imaging was performed on a 3.0 Tesla (T) MR scanner by using a rapid spoiled‐GRE protocol. T₁ measurement with driven equilibrium single pulse observation of T₁ (DESPOT1) was used to convert the MR signal to tracer concentration. Cerebral perfusion maps were obtained by using an improved gamma‐variate model in 10 subjects and compared with those with arterial spin label (ASL) approach.

Results:

The cerebral blood volume (CBV) values were calculated as 4.74 ± 1.09 and 2.29 ± 0.58 mL/100 g in gray matter (GM) and whiter matter (WM), respectively. Mean transit time (MTT) values were 6.15 ± 0.59 s in GM and 6.96 ± 0.79 s in WM. The DCE values for GM/WM cerebral blood flow (CBF) were measured as 53.41 ± 9.23 / 25.78 ± 8.91 mL/100 g/min, versus ASL values of 49.05 ± 10.81 / 23.00 ± 5.89 mL/100 g/min for GW/WM. Bland‐Altman plot revealed a small difference of CBF between two approaches (mean bias = 3.83 mL/100 g/min, SD = 11.29). There were 6 pairs of samples (5%, 6/120) beyond the 95% limits of agreement. The correlation plots showed that the slop of Y (CBF__DCE) versus X intercept (CBF__ASL) is 0.95 with the intercept of 4.53 mL/100 g/min (r = 0.74; P < 0.05).

Conclusion:

It is feasible to evaluate the cerebral perfusion by using T₁‐weighted DCE‐MRI with the improved kinetic model. J. Magn. Reson. Imaging 2012;35:1322–1331. © 2012 Wiley Periodicals, Inc.     

Vascular Dysfunction in Leukoaraiosis

BACKGROUND AND PURPOSE:The pathogenesis of leukoaraiosis has long been debated. This work addresses a less well-studied mechanism, cerebrovascular reactivity, which could play a leading role in the pathogenesis of this disease. Our aim was to evaluate blood flow dysregulation and its relation to leukoaraiosis.MATERIALS AND METHODS:Cerebrovascular reactivity, the change in the blood oxygen level–dependent 3T MR imaging signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide, was measured in white matter hyperintensities and their contralateral spatially homologous normal-appearing white matter in 75 older subjects (age range, 50–91 years; 40 men) with leukoaraiosis. Additional quantitative evaluation of regions of leukoaraiosis was performed by using diffusion (n = 75), quantitative T2 (n = 54), and DSC perfusion MRI metrics (n = 25).RESULTS:When we compared white matter hyperintensities with contralateral normal-appearing white matter, cerebrovascular reactivity was lower by a mean of 61.2% ± 22.6%, fractional anisotropy was lower by 44.9 % ± 6.9%, and CBF was lower by 10.9% ± 11.9%. T2 was higher by 61.7% ± 13.5%, mean diffusivity was higher by 59.0% ± 11.7%, time-to-maximum was higher by 44.4% ± 30.4%, and TTP was higher by 6.8% ± 5.8% (all P < .01). Cerebral blood volume was lower in white matter hyperintensities compared with contralateral normal-appearing white matter by 10.2% ± 15.0% (P = .03).CONCLUSIONS:Not only were resting blood flow metrics abnormal in leukoaraiosis but there is also evidence of reduced cerebrovascular reactivity in these areas. Studies have shown that reduced cerebrovascular reactivity is more sensitive than resting blood flow parameters for assessing vascular insufficiency. Future work is needed to examine the sensitivity of resting-versus-dynamic blood flow measures for investigating the pathogenesis of leukoaraiosis.

Age-related changes in the cerebral white matter are apparent on MR imaging. They appear as bright regions on T2-weighted images and are called white matter hyperintensities (WMH) if they are presumed to be of vascular origin. These areas are characterized by myelin pallor, reactive astrogliosis, and loss of oligodendrocytes, axons, and myelin fibers.¹ This rarefaction of white matter tissue is the origin of the term “leukoaraiosis,” derived from the Greek words “leuko-” for white and “araios” for rarefied.² As many as 95% of individuals older than 50 years of age demonstrate these white matter changes, particularly in the periventricular and deep white matter.^3,4 Once thought to represent benign age-related changes, studies during the past 25 years have shown that WMH are associated with morbidity, including cognitive impairment⁵ and disability.^6–8Substantial evidence indicates that age-related vascular changes may lead to WMH, including increased vessel tortuosity,⁹ increased stringed vessels (remnants of capillaries with no endothelial cells), and vessel basement membrane thickening.¹⁰ Histopathologic analysis of abnormal white matter shows venular intramural collagen deposition leading to wall-thickening stenosis.¹¹ The vascular anatomy of the white matter provides an intrinsically higher vascular resistance compared with the cortex.¹² Interestingly, white matter areas with excellent collateral blood supply, such as the subcortical U-fibers, do not usually show age-related WMH.¹³ Collectively, these findings suggest an association between vascular dysfunction and leukoaraiosis.In the present study, we sought to further characterize the vascular pathophysiology of WMH by evaluating cerebrovascular reactivity (CVR). CVR is defined as the change in cerebral blood flow induced by a vasoactive stimulus. Reduced CVR, normally found in the white matter of young healthy individuals,¹⁴ has been shown to spatially correspond with predilection maps of age-related leukoaraiosis development.¹⁵ CVR reductions are associated with cortical thinning,¹⁶ the risk of future ischemic stroke,¹⁷ cognitive decline,¹⁸ and abnormal diffusion tensor imaging metrics.¹⁹ WMH are associated with increased mean diffusivity (MD) and decreased fractional anisotropy, likely representing axonal destruction and glial proliferation.²⁰ Previous studies have found a relationship between impaired CVR and abnormal diffusion metrics in the white matter of patients with Moyamoya disease¹⁹ and steno-occlusive carotid disease,²¹ suggesting that chronic hypoperfusion is associated with pathologic changes to white matter microstructure. Moreover, vascular dysfunction in the form of blood-brain barrier leakage in WMH is also associated with increased MD.²²We evaluated CVR in regions of WMH and normal-appearing white matter (NAWM) by measuring the change in blood oxygen level–dependent (BOLD) MR imaging in response to a standard CO₂ challenge. To characterize the hemodynamic properties and microstructure of WMH, we obtained additional MR images and performed DTI and DSC perfusion MR imaging. We hypothesized that both CVR and these additional MR imaging metrics would differ between leukoaraiosis and NAWM.     

MR angiography of the cerebral perforating arteries with magnetization prepared anatomical reference at 7T: Comparison with time‐of‐flight

Purpose

To develop a magnetic resonance imaging (MRI) protocol that visualizes both the perforating arteries and the related anatomy in a single acquisition at 7T.

Material and Methods

T₁‐weighted magnetization prepared imaging (MPRAGE) was empirically modified for use as angiography method at 7T. The resulting sequence depicts the vasculature simultaneously with the surrounding anatomical structures, and is referred to as “magnetization prepared anatomical reference MRA” (MPARE‐MRA). The method was compared to time‐of‐flight (TOF) MRA in seven healthy subjects. The conspicuity of the perforating arteries and the contrast between gray and white matter were evaluated both quantitatively by contrast‐to‐noise (CNR) measurements, and qualitatively by two radiologists who scored the images.

Results

The contrast‐to‐noise ratio (CNR) between blood and background was 28 ± 9 for MPARE‐MRA and 35 ± 16 for TOF‐MRA, indicating good conspicuity of the vessels. CNR values were: internal capsule (IC) vs. caudate head (CH): 4.2 ± 0.7; IC vs. putamen: 3.5 ± 0.6; white matter vs. gray matter: 9.7 ± 2.5.

Conclusion

The benefits of ultra‐high‐field MRI can transform MPRAGE into a new angiography method to image small vessels and associated parenchyma at the same time. This technique can be used to study the correlation between tissue damage and vascular pathology. J. Magn. Reson. Imaging 2008;28:1519–1526. © 2008 Wiley‐Liss, Inc.     

Measurement of deep gray matter perfusion using a segmented true–fast imaging with steady‐state precession (True‐FISP) arterial spin‐labeling (ASL) method at 3T

Purpose

To study the feasibility of using the MRI technique of segmented true–fast imaging with steady‐state precession arterial spin‐labeling (True‐FISP ASL) for the noninvasive measurement and quantification of local perfusion in cerebral deep gray matter at 3T.

Materials and Methods

A flow‐sensitive alternating inversion‐recovery (FAIR) ASL perfusion preparation was used in which the echo‐planar imaging (EPI) readout was replaced with a segmented True‐FISP data acquisition strategy. The absolute perfusion for six selected regions of deep gray matter (left and right thalamus, putamen, and caudate) were calculated in 11 healthy human subjects (six male, five female; mean age = 35.5 years ± 9.9).

Results

Preliminary measurements of the average absolute perfusion values at the six selected regions of deep gray matter are in agreement with published values for mean absolute cerebral blood flow (CBF) baselines acquired from healthy volunteers using positron emission tomography (PET).

Conclusion

Segmented True‐FISP ASL is a practical and quantitative technique suitable to measure local tissue perfusion in cerebral deep gray matter at a high spatial resolution without the susceptibility artifacts commonly associated with EPI‐based methods of ASL. J. Magn. Reson. Imaging 2009;29:1425–1431. © 2009 Wiley‐Liss, Inc.     

Cerebral blood flow estimation in vivo using local tissue reference functions

Purpose

To evaluate the use of bolus signals obtained from tissue as reference functions (or local reference functions [LRFs]) rather than arterial input functions (AIFs) when deriving cross‐calibrated cerebral blood flow (CBF_CC) estimates via deconvolution.

Materials and Methods

AIF and white matter (WM) LRF CBF_CC maps (cross‐calibrated so that normal WM was 23.7 mL/minute/100 g) derived using singular value decomposition (SVD) were examined in 28 ischemic stroke patients. Median CBF_CC estimates from normal gray matter (GM) and ischemic tissue were obtained.

Results

AIF and LRF median CBF_CC estimates resembled one another for all 28 patients (average paired CBF_CC difference 0.4 ± 1.7 mL/minute/100 g and –0.4 ± 1.4 mL/minute/100 g in GM and ischemic tissue, respectively). Wilcoxon signed‐rank comparisons of patient median CBF_CC measurements revealed no statistically significant differences between using AIFs and LRFs (P > 0.05).

Conclusion

If CBF is quantified using a patient‐specific cross‐calibration factor, then LRF CBF estimates are at least as accurate as those from AIFs. Therefore, until AIF quantification is achievable in vivo, perfusion protocols tailored for LRFs would simplify the methodology and provide more reliable perfusion information. J. Magn. Reson. Imaging 2009;29:183–188. © 2008 Wiley‐Liss, Inc.     

Diffusional kurtosis imaging of normal-appearing white matter in multiple sclerosis: preliminary clinical experience

Purpose

We evaluated diffusional changes in normal-appearing white matter (NAWM) regions remote from multiple sclerosis (MS) plaques by using diffusional kurtosis imaging (DKI) to investigate the non-Gaussian behavior of water diffusion.

Materials and methods

Participants were 11 MS patients and 6 age-matched healthy volunteers. DKI was performed on a 3-T MR imager. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), and diffusional kurtosis (DK) maps were computed. Regions of interest (ROIs) were compared in 24 cerebral regions, including the frontal, parietal, and temporal lobe white matter (WM) in controls and NAWM in MS patients.

Results

The mean FA of all ROIs was 0.468 ± 0.014 (SD) (controls) or 0.431 ± 0.029 (MS group) (P = 0.016). Mean ADC was 0.785 ± 0.034 × 10^?3 mm²/s (controls) or 0.805 ± 0.041 × 10^?3 mm²/s (MS group). The mean DK of all ROIs was 0.878 ± 0.020 (controls) or 0.823 ± 0.032 (MS group) (P = 0.002). Analysis of individual ROIs revealed significant differences in DK in 3 ROIs between normal WM and NAWM, but significant differences in ADC and FA in only one ROI each.

Conclusion

DKI may be a new sensitive indicator for detecting tissue damage in MS patients in addition to conventional diffusional evaluations, for example diffusion tensor imaging.     

Use of ultrasmall superparamagnetic particles of iron oxide (USPIO)‐enhanced MRI to demonstrate diffuse inflammation in the normal‐appearing white matter (NAWM) of multiple sclerosis (MS) patients: An exploratory study

Purpose

To explore ultrasmall superparamagnetic particles of iron oxide (USPIO) as a marker for diffuse inflammation in multiple sclerosis (MS) normal‐appearing white matter (NAWM), using quantitative MRI. Disease activity in the NAWM of MS patients partly explains why MRI lesion burden correlates only moderately with disability. USPIO have been shown to visualize the cellular component of inflammation in focal MS lesions. In this study, we aimed to explore USPIO as a marker for the more diffuse inflammation in MS NAWM, using quantitative MRI.

Materials and Methods

In this prospective MRI study, 16 MS patients (eight relapsing‐remitting MS [RRMS] and eight primary‐progressive MS [PPMS] cases) and five healthy control (HC) subjects were included. Using a flip‐angle (FA) array, B1‐corrected T1 maps were generated before and 24 hours after USPIO (SHU555C) injection. White‐matter (WM) T1 histogram and region‐of‐interest (ROI) characteristics were compared between both time points using Wilcoxon signed‐rank test.

Results

Both NAWM ROI and histogram analyses showed T1 shortening after USPIO injection in MS patients (P < 0.01), but not in HCs (P = 0.68).

Conclusion

This exploratory study suggests that USPIO‐enhanced MRI may be a new potential marker for subtle inflammatory activity in MS NAWM. Further studies should focus on relating diffuse inflammation to clinical disease activity and treatment efficacy. J. Magn. Reson. Imaging 2009;29:774–779. © 2009 Wiley‐Liss, Inc.     

Using diffusion tensor imaging and immunofluorescent assay to evaluate the pathology of multiple sclerosis

Purpose:

To determine the ability of the principal diffusion tensor imaging (DTI) indices to predict the underlying histopathology evaluated with immunofluorescent assay (IFA).

Materials and Methods:

Conventional T2 and 3D multishot‐diffusion weighted echoplanar imaging (3D ms‐DWEPI) was performed on a fixed, ex vivo human cervical spinal cord (CSC) from a patient with a history of multiple sclerosis (MS). In all, 170 regions of interest (ROIs) were selected within the white matter and categorized as a high intensity lesion (HIL), low intensity lesion (LIL), and normal‐appearing white matter (NAWM). The longitudinal diffusivity (λl), radial diffusivity (λr), and fractional anisotropy (FA) were obtained from each ROI. The underlying histopathology was then evaluated using immunofluorescent assay with antibodies directed to myelin and neurofilament staining.

Results:

The mean values for λl and λr were significantly elevated within HIL relative to NAWM and LIL. IFA analysis of HIL demonstrated significant demyelination, without significant if any axon loss. The FA values were significantly reduced in HIL and LILs. FA values were also reduced in lesions with increased λl and λr values relative to normal.

Conclusion:

Aberrant λl, λr, and FA relative to normal values are strong indicators of demyelination. DTI indices are not specific for axon loss. IFA analysis is a reliable method to demonstrate myelin and axon pathology within the ex vivo setting. J. Magn. Reson. Imaging 2011;33:557–564. © 2011 Wiley‐Liss, Inc.     

Characterization of low‐grade gliomas using RGB color maps derived from ADC histograms

Purpose

To use normalized apparent diffusion coefficient (nADC) histograms from patients with grade II oligodendroglioma (OD) and astrocytoma (AC) to generate RGB color maps that emphasize the differences between normal‐appearing white matter (NAWM), oligo‐like, and astro‐like regions.

Materials and Methods

NAWM and nonenhancing lesion (NEL) ADC values from 19 ODs and 11 ACs were summed to generate oligo‐like (red), NAWM (green), and astro‐like (blue) nADC histograms. These nADC histograms were then used to map nADC values to an RGB matrix.

Results

Color maps of oligodendroglial tumor regions were generally visualized in pink, while color maps of astrocytic tumor regions showed various shades of blue. This technique was also applied to 23 patients with the more mixed subtype, oligoastrocytoma (OA), which showed a mixture of both blue and pink, which in many cases appeared to bleed into each other and were blotchy.

Conclusion

This technique allows for the visualization of biologically different regions within the whole tumor mass, which may aid in directing image‐guided biopsies. This can be used to ensure that the biopsy is directed to regions that can more accurately define the dominant tumor characteristics. J. Magn. Reson. Imaging 2009;30:209–213. © 2009 Wiley‐Liss, Inc.     

Quantitative measurement of blood‐brain barrier permeability in human using dynamic contrast‐enhanced MRI with fast T1 mapping

Breakdown of the blood‐brain barrier (BBB), occurring in many neurological diseases, has been difficult to measure noninvasively in humans. Dynamic contrast‐enhanced magnetic resonance imaging measures BBB permeability. However, important technical challenges remain and normative data from healthy humans is lacking. We report the implementation of a method for measuring BBB permeability, originally developed in animals, to estimate BBB permeability in both healthy subjects and patients with white matter pathology. Fast T₁ mapping was used to measure the leakage of contrast agent Gadolinium diethylene triamine pentaacetic acid (Gd‐DTPA) from plasma into brain. A quarter of the standard Gd‐DTPA dose for dynamic contrast‐enhanced magnetic resonance imaging was found to give both sufficient contrast‐to‐noise and high T₁ sensitivity. The Patlak graphical approach was used to calculate the permeability from changes in 1/T₁. Permeability constants were compared with cerebrospinal fluid albumin index. The upper limit of the 95% confidence interval for white matter BBB permeability for normal subjects was 3 × 10^?4 L/g min. MRI measurements correlated strongly with levels of cerebrospinal fluid albumin in those subjects undergoing lumbar puncture. Dynamic contrast‐enhanced magnetic resonance imaging with low dose Gd‐DTPA and fast T₁ imaging is a sensitive method to measure subtle differences in BBB permeability in humans and may have advantages over techniques based purely on the measurement of pixel contrast changes. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Relationships of brain white matter microstructure with clinical and MR measures in relapsing‐remitting multiple sclerosis

Purpose:

To assess the relationships of microstructural damage in the cerebral white matter (WM), as measured by diffusion tensor imaging (DTI), with clinical parameters and magnetic resonance imaging (MRI) measures of focal tissue damage in patients with multiple sclerosis (MS).

Materials and Methods:

Forty‐five relapsing‐remitting (RR) MS patients (12 male, 33 female; median age = 29 years, Expanded Disability Status Scale (EDSS) = 1.5, disease duration = 3 years) were studied. T2‐lesion masks were created and voxelwise DTI analyses performed with Tract‐Based Spatial Statistics (TBSS).

Results:

T2‐lesion volume (T2‐LV) was significantly (P < 0.05, corrected) correlated with fractional anisotropy (FA) in both lesions and normal‐appearing WM (NAWM). Relationships (P = 0.08, corrected) between increasing EDSS score and decreasing FA were found in the splenium of the corpus callosum (sCC) and along the pyramidal tract (PY). All FA associations were driven by changes in the perpendicular (to primary tract direction) diffusivity. No significant global and voxelwise FA changes were found over a 2‐year follow‐up.

Conclusion:

FA changes related to clinical disability in RR‐MS patients with minor clinical disability are localized to specific WM tracts such as the sCC and PY and are driven by changes in perpendicular diffusivity both within lesions and NAWM. Longitudinal DTI measurements do not seem able to chart the early disease course in the WM of MS patients. Imaging 2010; 31:309–316. © 2010 Wiley‐Liss, Inc.     

Dynamic susceptibility contrast perfusion weighted imaging in grading of nonenhancing astrocytomas

Purpose

To evaluate if the relative tumor blood volume (rTBV) using dynamic susceptibility contrast magnetic resonance imaging (DSC‐MRI) can aid in distinguishing low‐ from high‐grade nonenhancing astrocytomas.

Materials and Methods

Seventeen patients with histologically proven astrocytomas underwent MRI including DSC‐MRI. Maximum TBV regions of interest were recorded from each neoplasm and normalized to contralateral normal white matter. Demographic features, diagnostic MRI findings including tumor volumes, and the normalized rTBV ratios were compared between low‐grade (I and II, LGA, n = 6) and high‐grade (III) astrocytomas (HGA, n = 11) using Mann–Whitney's U‐test and receiver operating characteristic (ROC) analysis.

Results

Maximum rTBV ratios were statistically higher for HGA (1.11 ± 0.13) than LGA (0.66 ± 0.17, P < 0.005) with the best cutoff threshold at 0.94 (sensitivity of 90.9%, specificity of 100%). Differences in mean age and tumor volume on fluid‐attenuated inversion recovery (FLAIR) imaging between the two groups did not reach statistical difference (P = 0.22, 0.36).

Conclusion

The addition of DSC‐MRI can aid in accurate grading of nonenhancing astrocytomas with high sensitivity and specificity. J. Magn. Reson. Imaging 2010;32:803–808. © 2010 Wiley‐Liss, Inc.     

Measuring the neural response to continuous intramuscular infusion of hypertonic saline by perfusion MRI

Purpose:

To determine the extent to which arterial spin labeling (ASL), a functional magnetic resonance imaging technique that directly measures cerebral blood flow (CBF), is able to measure the neural activation associated with prolonged experimental muscle pain.

Materials and Methods:

Hypertonic saline (HS) (5% NaCl) was infused into the brachioradialis muscle of 19 healthy volunteers for 15 min. The imaging volume extended from the dorsal side of the pons to the primary somatosensory cortices, covering most of the cortical and subcortical regions associated with pain perception.

Results:

Using a numerical scale from 0 to 10, ratings of pain intensity peaked at 5.9 ± 0.5 (mean ± SE). Group activation maps showed that the slow infusion of HS evoked CBF increases primarily in bilateral insula, with additional activation in right frontal regions. In the activated areas, CBF gradually increased at the onset of HS infusion and was maintained at relatively constant levels throughout the remainder of the infusion period. However, the level and extent of activation were smaller than observed in previous studies involving acute muscle pain.

Conclusion:

This study demonstrates the ability of ASL to measure changes in CBF over extended periods of time and that the neural activation caused by muscle pain is paradigm specific. J. Magn. Reson. Imaging 2012;35:669‐677. © 2011 Wiley‐Liss, Inc.     

Comparison of spiral imaging and SENSE‐EPI at 1.5 and 3.0 T using a controlled cerebrovascular challenge

Purpose

To quantitatively compare spiral imaging and sensitivity‐encoded‐echo‐planar‐imaging (SENSE‐EPI) methods for blood oxygen level‐dependent (BOLD) imaging using controlled changes in the end‐tidal partial pressure of CO₂ (PetCO₂) to provide a global BOLD response. Specifically, we examined susceptibility‐field‐gradient effects on the BOLD sensitivity throughout the brain.

Materials and Methods

We quantified cerebrovascular reactivity (CVR) using the BOLD response to cyclic changes in PetCO₂ in five healthy volunteers at 1.5 and 3.0 T using spiral imaging and SENSE‐EPI. We compared the two techniques with respect to susceptibility‐induced signal dropout and CVR t‐statistic.

Results

Compared to spiral imaging, SENSE‐EPI significantly reduced the volume of signal dropout by 32 ± 18% at 3.0 T. In regions with large susceptibility gradients, SENSE‐EPI demonstrated a trend for a greater t‐statistic than spiral imaging, particularly at 3.0 T. However, no statistically significant between‐technique differences existed.

Conclusion

The results at 3.0 T suggest that, compared with spiral imaging, SENSE‐EPI reduces signal loss associated with susceptibility field gradients in affected regions without affecting BOLD sensitivity. This study also demonstrates a unique application of controlled PetCO₂ changes to quantitatively compare BOLD techniques, which may be useful for the design of future fMRI studies. J. Magn. Reson. Imaging 2009;29:1206–1210. © 2009 Wiley‐Liss, Inc.     

Improving dynamic susceptibility contrast MRI measurement of quantitative cerebral blood flow using corrections for partial volume and nonlinear contrast relaxivity: A xenon computed tomographic comparative study

Purpose

To test whether dynamic susceptibility contrast MRI‐based CBF measurements are improved with arterial input function (AIF) partial volume (PV) and nonlinear contrast relaxivity correction, using a gold‐standard CBF method, xenon computed tomography (xeCT).

Materials and Methods

Eighteen patients with cerebrovascular disease underwent xeCT and MRI within 36 h. PV was measured as the ratio of the area under the AIF and the venous output function (VOF) concentration curves. A correction was applied to account for the nonlinear relaxivity of bulk blood (BB). Mean CBF was measured with both techniques and regression analyses both within and between patients were performed.

Results

Mean xeCT CBF was 43.3 ± 13.7 mL/100g/min (mean ± SD). BB correction decreased CBF by a factor of 4.7 ± 0.4, but did not affect precision. The least‐biased CBF measurement was with BB but without PV correction (45.8 ± 17.2 mL/100 g/min, coefficient of variation [COV] = 32%). Precision improved with PV correction, although absolute CBF was mildly underestimated (34.3 ± 10.8 mL/100 g/min, COV = 27%). Between patients correlation was moderate even with both corrections (R = 0.53).

Conclusion

Corrections for AIF PV and nonlinear BB relaxivity improve bolus MRI‐based CBF maps. However, there remain challenges given the moderate between‐patient correlation, which limit diagnostic confidence of such measurements in individual patients. J. Magn. Reson. Imaging 2009;30:743–752. © 2009 Wiley‐Liss, Inc.     

Validity of apparent diffusion coefficient (ADC) value in diagnosis and follow-up of multiple sclerosis patients in different clinical subtypes

Background

Multiple sclerosis (MS) is a chronic disease with a wide range of pathologic changes that modify the apparent diffusion coefficient (ADC) value.

Perfusion MRI in neuro‐psychiatric systemic lupus erthemathosus

Purpose:

To use perfusion weighted MR to quantify any perfusion abnormalities and to determine their contribution to neuropsychiatric (NP) involvement in systemic lupus erythematosus (SLE).

Materials and methods:

We applied dynamic susceptibility contrast (DSC) perfusion MRI in 15 active NPSLE, 26 inactive NPSLE patients, and 11 control subjects. Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were reconstructed and regions of interest were compared between groups. In addition, the effect of SLE criteria, NPSLE syndromes, immunological coagulation disorder, and medication on CBF, CBV, and MTT was investigated.

Results:

No significant differences were found between the groups in CBF, CBV, and MTT. No significant influence of SLE criteria or NPSLE syndromes on CBF, CBV, or MTT was found. No significant influence of anti‐cardiolipin antibodies, lupus anti‐coagulant, the presence of anti‐phospholipid syndrome (APS), or medication on CBF, CBV, or MTT was found.

Conclusion:

Our findings suggest CBF, CBV, and MTT in the white and the gray matter in SLE patients is not significantly different from healthy controls or between patients with and without specific symptoms or with and without immunological disorder involving coagulation. J. Magn. Reson. Imaging 2010;32:283–288. © 2010 Wiley‐Liss, Inc.