Validating the sensitivity of inhomogeneous magnetization transfer (ihMT) MRI to myelin with fluorescence microscopy.

Inhomogeneous Magnetization Transfer (ihMT) is a development from the MT MRI technique. IhMT can be considered as a dipolar order relaxation time (T1D) weighted imaging modality whose signal has shown an enhanced selectivity for myelin-rich structures. However, a formal validation of the ihMT sensitivity relative to a gold standard myelin density measurement has not yet been reported. To address this need, we compared ihMT MRI with green fluorescence protein (GFP) microscopy, in a study performed on genetically-modified plp-GFP mice, considered as a reference technique for myelin-content assessment. Various ihMT protocols consisting of variable T1D-filtering and radiofrequency power temporal distributions, were used for comparison with fluorescence microscopy. Strong and significant linear relationships (r2 (0.87-0.96), p < 0.0001) were found between GFP and ihMT ratio signals across brain regions for all tested protocol variants. Conventional MT ratios showed weaker correlations (r2 (0.24-0.78), p ≤ 0.02) and a much larger signal fraction unrelated to myelin, hence corresponding to a much lower specificity for myelin. T1D-filtering reduced the ihMT signal fraction not attributed to myelin by almost twofold relative to zero filtering suggesting that at least half of the unrelated signal has a substantially shorter T1D than myelin. Overall, these results strongly support the sensitivity of ihMT to myelin content.

Optimization of inhomogeneous magnetization transfer (ihMT) MRI contrast for preclinical studies using dipolar relaxation time (T1D ) filtering.

A pulsed inhomogeneous magnetization transfer (ihMT)-prepared fast imaging sequence was implemented at 11.75 T for preclinical studies on mouse central nervous system. A strategy based on filtering the ihMT signal originating from short dipolar relaxation time (T1D ) components is proposed. It involves increasing the repetition time of consecutive radiofrequency (RF) pulses of the dual saturation and allows improved signal specificity for long T1D myelinated structures. Furthermore, frequency offset, power and timing saturation parameters were adjusted to optimize the ihMT sensitivity. The optimization of the ihMT sensitivity, whilst preserving the strong specificity for the long T1D component of myelinated tissues, allowed measurements of ihMT ratios on the order of 4-5% in white matter (WM), 2.5% in gray matter (GM) and 1-1.3% in muscle. This led to high relative ihMT contrasts between myelinated tissues and others (~3-4 between WM and muscle, and ≥2 between GM and muscle). Conversely, higher ihMT ratios (~6-7% in WM) could be obtained using minimal T1D filtering achieved with short saturation pulse repetition time or cosine-modulated pulses for the dual-frequency saturation. This study represents a first stage in the process of validating ihMT as a myelin biomarker by providing optimized ihMT preclinical sequences, directly transposable and applicable to other preclinical magnetic fields and scanners. Finally, ihMT ratios measured in various central nervous system areas are provided for future reference.

Resting-state cerebral blood flow in amygdala is modulated by sex and serotonin transporter genotype.

Serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with modulation of resting-state amygdala level, which was considered to underlie a risk for mood and anxiety disorders. The findings however have been inconsistent which could be related to interactions of the genotype with other factors e.g. sex or personality characteristics. Therefore, the aim of the present study was to explore the modulation of the amygdala perfusion in the resting-state by sex and 5-HTTLPR/rs25531 genotype, controlled for personality dimensions assessed by Temperament and Character Inventory (Cloninger et al., 1994). The resting-state cerebral blood flow (rCBF) was examined using an arterial spin labelling technique. All participants were genotyped for the 5-HTTLPR/rs25531 genotype (L/L-L/S-S/S genotypes and LA-LG variants). The study group comprised 81 right-handed Caucasian healthy volunteers (42 females) aged 19-55 years. We measured rCBF in the amygdala and in the whole-brain grey matter. The data of blood-oxygen-level-dependent (BOLD) response in amygdala to fearful dynamic faces in the same sample were also analysed. There was a significant main effect of sex in both the left and right amygdalae, with higher rCBF in males. Main effect of 5-HTTLPR/rs25531 genotype which was significant in the right amygdala only, was accounted for by higher rCBF in S/S vs. L/L homozygotes. An interaction between sex and 5-HTTLPR/rs25531 genotype was observed in rCBF in the right amygdala. This was accounted for by higher values of rCBF in the right amygdala in males' S allele carriers compared with females. In females, there was a significant negative correlation between the rCBF and BOLD response in the right amygdala, and more so in S carriers. In males, there was no significant correlation between rCBF and BOLD response in the right amygdala. The novelty of our results lies in the demonstration of gene by sex interaction with resting blood flow in the amygdala that elucidates sex-related differences in emotional reactivity.

Cox-2 inhibition enhances the activity of sunitinib in human renal cell carcinoma xenografts.

BACKGROUND: Sunitinib (Su), a tyrosine kinase inhibitor of VEGFR, is effective at producing tumour response in clear cell renal cell carcinoma (cRCC), but resistance to therapy is inevitable. As COX-2 is a known mediator of tumour growth, we explored the potential benefit of COX-2 inhibition in combination with VEGFR inhibition in attempts at delaying tumour progression on Su. METHODS: COX-2 expression was compared with areas of hypoxia in tumours that progressed on Su vs untreated tumours. Mice bearing human cRCC xenografts were treated with Su and the COX-2 inhibitor, celecoxib, and the effects on tumour growth were assessed. Sequential vs concurrent regimens were compared. RESULTS: COX-2 expression was increased in cRCC xenografts in areas of tumour hypoxia. The combination of Su and celecoxib achieved longer times to tumour progression compared to treatment with either agent alone or to untreated control animals in four models. This effect was seen with concurrent but not with sequential therapy. CONCLUSION: COX-2 inhibition can extend the effectiveness of VEGFR inhibition. This effect is dependent on the timing of therapy. Clinical trials combining Su and COX-2 inhibitors should be considered as a means delaying time to progression on sunitinib in patients with metastatic cRCC.

Coupling between resting cerebral perfusion and EEG.

While several studies have investigated interactions between the electroencephalography (EEG) and functional magnetic resonance imaging BOLD signal fluctuations, less is known about the associations between EEG oscillations and baseline brain haemodynamics, and few studies have examined the link between EEG power outside the alpha band and baseline perfusion. Here we compare whole-brain arterial spin labelling perfusion MRI and EEG in a group of healthy adults (n = 16, ten females, median age: 27 years, range 21-48) during an eyes closed rest condition. Correlations emerged between perfusion and global average EEG power in low (delta: 2-4 Hz and theta: 4-7 Hz), middle (alpha: 8-13 Hz), and high (beta: 13-30 Hz and gamma: 30-45 Hz) frequency bands in both cortical and sub-cortical regions. The correlations were predominately positive in middle and high-frequency bands, and negative in delta. In addition, central alpha frequency positively correlated with perfusion in a network of brain regions associated with the modulation of attention and preparedness for external input, and central theta frequency correlated negatively with a widespread network of cortical regions. These results indicate that the coupling between average EEG power/frequency and local cerebral blood flow varies in a frequency specific manner. Our results are consistent with longstanding concepts that decreasing EEG frequencies which in general map onto decreasing levels of activation.

Low duty-cycle pulsed irradiation reduces magnetization transfer and increases the inhomogeneous magnetization transfer effect.

Intense off-resonant RF irradiation can lead to saturation of the macromolecular pool magnetization and enhance bound pool dipolar order responsible for the inhomogeneous magnetization transfer (ihMT) effect, but the intensity of RF power in human imaging studies is limited by safety constraints on RF heating. High RF intensities can still be achieved if applied in short pulses with low duty-cycle. Here we investigate the benefits of low duty-cycle irradiation for MT and ihMT studies with both theoretical and experimental methods. Solutions for pulsed irradiation of a two-pool model including dipolar order effects were implemented. Experiments were conducted at 3 T in the brain and through the calf of healthy human subjects. 2D echo planar images were acquired following a preparation of RF irradiation with a 2 s train of 5 ms pulses repeated from between 10 to 100 ms for duty-cycles (DCs) of 50% to 5%, and at varying offset frequencies, and time averaged RF powers. MT and ihMT data were measured in regions of interest within gray matter, white matter and muscle, and fit to the model. RF irradiation effects on signal intensity were reduced at 5% relative to 50% DCs. This reduced RF effect was much larger for single than dual frequency irradiation. 5% DC irradiation reduced single and dual frequency MT ratios but increased ihMT ratios up to 3 fold in brain tissues. Muscle ihMT increased by an even larger factor, depending on the frequency and applied power. The model predicted these changes with duty-cycle. The model fit the data well and constrained model parameters. Low duty-cycle pulsed irradiation reduces MT effects and markedly increases dipolar order effects. This approach is an attractive method to enhance ihMT signal-to-noise ratio and demonstrates a measurable ihMT effect in muscle tissue at 3 T under acceptable specific absorption rates. The effects of duty-cycle changes demonstrated in a separate MT/ihMT preparation provide a route for new applications in magnetization-prepared MRI sequences.

Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis.

BACKGROUND AND PURPOSE: Inhomogeneous magnetization transfer is a new endogenous MR imaging contrast mechanism that has demonstrated high specificity for myelin. Here, we tested the hypothesis that inhomogeneous magnetization transfer is sensitive to pathology in a population of patients with relapsing-remitting MS in a way that both differs from and complements conventional magnetization transfer. MATERIALS AND METHODS: Twenty-five patients with relapsing-remitting MS and 20 healthy volunteers were enrolled in a prospective MR imaging research study, whose protocol included anatomic imaging, standard magnetization transfer, and inhomogeneous magnetization transfer imaging. Magnetization transfer and inhomogeneous magnetization transfer ratios measured in normal-appearing brain tissue and in MS lesions of patients were compared with values measured in control subjects. The potential association of inhomogeneous magnetization transfer ratio variations with the clinical scores (Expanded Disability Status Scale) of patients was further evaluated. RESULTS: The magnetization transfer ratio and inhomogeneous magnetization transfer ratio measured in the thalami and frontal, occipital, and temporal WM of patients with MS were lower compared with those of controls (P < .05). The mean inhomogeneous magnetization transfer ratio measured in lesions was lower than that in normal-appearing WM (P < .05). Significant (P < .05) negative correlations were found between the clinical scores and inhomogeneous magnetization transfer ratio measured in normal-appearing WM structures. Weaker nonsignificant correlation trends were found for the magnetization transfer ratio. CONCLUSIONS: The sensitivity of the inhomogeneous magnetization transfer technique for MS was highlighted by the reduction in the inhomogeneous magnetization transfer ratio in MS lesions and in normal-appearing WM of patients compared with controls. Stronger correlations with the Expanded Disability Status Scale score were obtained with the inhomogeneous magnetization transfer ratio compared with the standard magnetization transfer ratio, which may be explained by the higher specificity of inhomogeneous magnetization transfer for myelin.

Interpretation of magnetization transfer from inhomogeneously broadened lines (ihMT) in tissues as a dipolar order effect within motion restricted molecules.

Comparison of off-resonance saturation with single and dual frequency irradiation indicates a contribution of inhomogeneously broadened lines to magnetization transfer in tissues. This inhomogeneous magnetization transfer (ihMT) phenomenon can be exploited to produce images that highlight tissues containing myelin, in vivo. Here, a model for ihMT is described that includes dipolar order effects from magnetization associated with motion-restricted macromolecules. In this model, equal irradiation at positive and negative frequency offsets eliminates dipolar order and achieves greater saturation than irradiation at a single offset frequency using the same power. Fitting of mouse and human volunteer brain data at different irradiation powers and offset frequencies was performed to assess the relevance of the model and approximate tissue parameters. A key parameter in determining ihMT signal was found to be the relaxation time T1D associated with the dipolar order reservoir and the fraction f of the semi-solid, bound magnetization that possessed a nonzero T1D. Indeed, better fits of myelinated tissue were achieved when assuming f≠1. From such fits, estimated T1Ds of mice in the white matter, (34±14) ms, were much longer than in muscle, T1D=(1±1) ms and the average f from white matter volunteer data was 2.2 times greater than that in grey matter. The combination of f and longer T1Ds was primarily responsible for the much higher ihMT in myelinated tissues, and provided explanation for the species variation. This dipolar order ihMT model should help guide future research, pulse sequence optimization, and clinical applications.

Reduced transit-time sensitivity in noninvasive magnetic resonance imaging of human cerebral blood flow.

Herein, we present a theoretical framework and experimental methods to more accurately account for transit effects in quantitative human perfusion imaging using endogenous magnetic resonance imaging (MRI) contrast. The theoretical transit time sensitivities of both continuous and pulsed inversion spin tagging experiments are demonstrated. We propose introducing a delay following continuous labeling, and demonstrate theoretically that introduction of a delay dramatically reduces the transit time sensitivity of perfusion imaging. The effects of magnetization transfer saturation on this modified continuous labeling experiment are also derived, and the assumption that the perfusion signal resides entirely within tissue rather than the arterial microvasculature is examined. We present results demonstrating the implementation of the continuous tagging experiment with delay on an echoplanar scanner for measuring cerebral blood flow (CBF) in normal volunteers. By varying the delay, we estimate transit times in the arterial system, values that are necessary for assessing the accuracy of our quantification. The effect of uncertainties in the transit time from the tagging plane to the arterial microvasculature and the transit time to the tissue itself on the accuracy of perfusion quantification is discussed and found to be small in gray matter but still potentially significant in white matter. A novel method for measuring T1, which is fast, insensitive to contamination by cerebrospinal fluid, and compatible with the application of magnetization transfer saturation, is also presented. The methods are combined to produce quantitative maps of resting and hypercarbic CBF.

Noninvasive MRI evaluation of cerebral blood flow in cerebrovascular disease.

Previous studies have demonstrated that cerebral blood flow (CBF) can be assessed noninvasively by MRI using magnetic labeling of arterial water as a diffusible flow tracer. The purpose of this study was to assess the quality of CBF images obtained from patients with cerebrovascular disease using this method, and to begin to evaluate the potential clinical role for this technique. We recruited 14 patients who presented with stroke, TIA, or severe carotid stenosis and were likely to have altered CBF based on clinical assessment. In many of these patients, CBF imaging disclosed both focal and hemispheric hypoperfusion, either in vascular territories or in watershed regions. In 11 patients with significant proximal arterial stenosis, hemispheric CBF abnormalities localized to the side of most significant stenosis for the anterior circulation distribution. In several patients watershed hypoperfusion was even more pronounced. Our results suggest that good-quality MR CBF images can be obtained reliably from patients with cerebrovascular disease. CBF imaging can be combined with standard structural imaging within a single MRI examination, and provides clinically meaningful information. The capability of measuring CBF easily provides a potentially useful tool for clinical assessment and further investigation of stroke pathophysiology.

Functional MRI lateralization of memory in temporal lobe epilepsy.

OBJECTIVE: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. METHODS: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. RESULTS: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.

A functional MRI study of mental image generation.

The neural substrates of mental image generation were investigated with functional MRI. Subjects listened to words under two different instructional conditions: to generate visual mental images of the words' referents, or to simply listen to each word and wait for the next word. Analyses were performed which directly compared the regional brain activity during each condition, with the goal of discovering whether mental image generation engages modality-specific visual areas, whether it engages primary visual cortex, and whether it recruits the left hemisphere to a greater extent than the right. Results revealed that visual association cortex, and not primary visual cortex, was engaged during the mental image generation condition. Left inferior temporal lobe (Brodmann's area 37) was the most reliably and robustly activated area across subjects, had activity which extended superiorly into occipital association cortex (area 19). The results of this experiment support the hypothesis that visual mental imagery is a function of visual association cortex, and that image generation is asymmetrically localized to the left.

Detection of acute pathologic changes following experimental traumatic brain injury using diffusion-weighted magnetic resonance imaging.

Standard magnetic resonance imaging (MRI) has been shown to be remarkably insensitive to acute changes following traumatic brain injury. Because diffusion-weighted MRI has recently demonstrated excellent sensitivity to acute ischemic injury and other CNS abnormalities, we evaluated the use of diffusion MRI for the detection of pathologic changes in the rat brain during the first hours following parasagittal fluid percussion brain injury. Diffusion MRI was able to demonstrate a significant diffusion decrease in the primary cortical contusion injury and a comparable decrease in the ipsilateral thalamus. Tissue damage in the thalamus region is much weaker than in the cortex, but the thalamus is a primary site of axonal and dendritic injury in this model. T2 imaging in the same subjects showed slight enhancement in the neighborhood of the injured cortex but was unable to demonstrate injury elsewhere. Diffusion imaging was superior to T2 at demonstrating injury and the prominent diffusion decrease in the thalamus suggests that diffusion MRI is preferentially sensitive to axonal or dendritic injury.

New magnetic resonance imaging techniques for the evaluation of traumatic brain injury.

Although current computerized tomography (CT) and magnetic resonance imaging (MRI) techniques have shown great utility in diagnosing various aspects traumatic brain injury, damage resulting from mild diffuse brain injury often goes undetected with these procedures. Newly developed MRI techniques, including magnetization transfer imaging (MTI) and diffusion-weighted imaging (DWI), have been proposed to have enhanced sensitivities for identifying damage induced by both diffuse and focal brain injury. Results from recent initial studies with experimental models of brain injury suggest that MTI may be useful for evaluating diffuse white matter damage, while DWI may demonstrate regions of focal contusion more acutely and with greater accuracy than conventional MRI procedures.

Mapping of secondary somatosensory cortex activation induced by vibrational stimulation: an fMRI study.

Sensory functional MRI was performed in seven normal volunteers at 1. 5 T using a vibratory stimulus applied to the pad of the first finger of the left hand. The data was normalized to a standard atlas, and individual and group statistical parametric maps were computed. Robust bilateral activation was demonstrated in the secondary somatosensory cortex (SII), indicating a bilateral representation of SII in humans. Greater maxima and activation volumes were achieved in contralateral SII as compared to SI. Sensory fMRI can provide a sensitive assay for probing the nature and function of SII in vivo.

Gender effects on odor-stimulated functional magnetic resonance imaging.

On standardized tests of odor identification and odor detection, women tend to score better than men at nearly all age groups. We sought to determine if these findings would translate to differences between the sexes in the volume of activated brain when odors are presented to subjects as the stimulants for functional magnetic resonance imaging (FMRI) experiments. The activation maps of eight right-handed women (mean age 25.3 years old, range 20-44, S.D. 8.3 years) were compared with those of 8 right-handed men (mean age 30.5, range 18-37, S.D. 6.5 years) given the same olfactory nerve stimuli in an FMRI experiment at 1.5 T. Olfactory stimuli were delivered to the patients in a passive fashion using a Burghart OM4-B olfactometer with a nose piece inserted into the patients' nostrils. We used agents (eugenol, phenyl ethyl alcohol, or phenyl ethyl alcohol alternating with hydrogen sulfide) that were selective for olfactory nerve stimulation in the nose. The odorants were delivered to both nostrils for 1 s every 4 s during a 30 s 'on-period'. During the 30 s 'off-period', the patient received room air at the same flow rate. The women's group-averaged activation maps showed up to eight times more activated voxels than men for specific regions of the brain (frontal and perisylvian regions). The left and right inferior frontal regions showed a statistically significant increase in activation in women at p<0.01. In general, more women showed activation than men. The results suggest that (1) FMRI activation maps in subject groups can demonstrate correlates to psychophysical tests of olfaction, and (2) one must control for gender when performing odor-stimulated FMRI experiments.

The effect of age on odor-stimulated functional MR imaging.

BACKGROUND AND PURPOSE: The effects of age, sex, and handedness on olfaction have not been adequately addressed with odor-stimulated functional MR imaging studies. We sought to determine the effect of age on functional MR imaging experiments performed with odor stimulation. METHODS: Five right-handed subjects with a mean age of 73 years and five right-handed subjects with a mean age of 24 years underwent gradient-echo echo-planar functional MR imaging using binasal olfactory stimulation. Imaging parameters included 3000/30 (TR/TE) and a 5-mm section thickness in a 6-minute sequence with 30 seconds of pulsed odorants alternating with 30 seconds of room air. The data were normalized to a standard atlas, and individual and group statistical parametric maps (SPMs) were generated for each task. The SPMs were thresholded for a P < .01, and the volumes of activation and distribution of cluster maxima were compared for the two groups. RESULTS: Analysis of the group SPMs revealed activated voxels in the frontal lobes, perisylvian regions, and cingulate gyri, with greater volume in the younger group than in the older group. The right inferior frontal, right perisylvian, and right and left cingulum had the largest number of voxels activated. The most common sites of activation on individual maps in both groups were the right inferior frontal regions and the right and left superior frontal and perisylvian zones. CONCLUSION: Given similar olfactory task paradigms, younger subjects showed a greater number of activated voxels than did older subjects. One must be cognizant of this effect when designing studies of odor-stimulated functional MR imaging.

Detection of mesial temporal lobe hypoperfusion in patients with temporal lobe epilepsy by use of arterial spin labeled perfusion MR imaging.

BACKGROUND AND PURPOSE: Interictal hypometabolism has lateralizing value in cases of temporal lobe epilepsy and positive predictive value for seizure-free outcome after surgery to treat epilepsy. Alterations in regional cerebral metabolism can also be inferred from measurements of regional cerebral perfusion. The purpose of this study was to determine the feasibility of detecting cerebral blood flow (CBF) asymmetries in the mesial temporal lobes using continuous arterial spin labeling perfusion MR imaging, which is a noninvasive method for calculating regional CBF. METHODS: Twelve patients with medically refractory temporal lobe epilepsy who underwent preoperative evaluation for temporal lobectomy and 12 normal control participants were studied retrospectively. Absolute and normalized mesial temporal CBF measurements were compared between the patient and control groups. Lateralization based on a perfusion asymmetry index was compared with metabolic ((18)[F]-fluorodeoxyglucose positron emission tomography) and hippocampal volumetric asymmetry indices and with clinical lateralization. RESULTS: Mesial temporal CBF was more asymmetric in patients with temporal lobe epilepsy than in normal control participants, although asymmetric mesial temporal CBF was also found in normal participants, with the left side dominant. Ipsilateral mesial temporal CBF was significantly decreased compared with contralateral mesial temporal CBF in patients with temporal lobe epilepsy. Global CBF measurements were significantly decreased in patients compared with control participants. Asymmetry in mesial temporal blood flow in patients persisted after normalization to global CBF. Lateralization using continuous arterial spin labeling perfusion MR imaging asymmetry index significantly correlated with lateralization based on (18)[F]-fluorodeoxyglucose positron emission tomography hypometabolism, hippocampal volumes, and clinical evaluation. CONCLUSION: Continuous arterial spin labeling perfusion MR imaging can detect interictal asymmetries in mesial temporal lobe perfusion in patients with temporal lobe epilepsy. This technique is readily combined with routine structural assessment and potentially offers an inexpensive and noninvasive means of screening for asymmetries in interictal mesial temporal lobe function.

Correlation of diffusion MRI and heat shock protein in a rat embolic stroke model.

The expression of 70 kDa heat shock protein (HSP-70) in focal ischemia occurs in regions that sustain sub-lethal ischemic injury, and may therefore be considered as a biological marker of the ischemic penumbra. In a rat embolic stroke model, using fibrin-rich emboli, we correlated the expression of HSP-70 mRNA with diffusion magnetic resonance imaging (MRI) to determine if HSP-70 mRNA expression was associated with alterations in the apparent diffusion coefficient (ADC) of brain tissue water, a putative early marker of cytotoxic injury that is readily measured in vivo. Serial ADC measurements were made for 120 min following embolic infarction in the right carotid artery territory. HSP-70 mRNA expression was observed at the boundaries of the densely ischemic zone, as judged by diffusion imaging. ADC values observed in HSP-70 mRNA-positive regions were intermediate between those observed in the ischemic core or in control regions. In addition, the volume of HSP-70 mRNA-positive tissue correlated positively with the volume of tissue showing intermediate ADC values at 120 min. These findings suggest that intermediate ADC values occur in penumbral regions. Heterogeneity of ischemic cellular injury is suggested as the basis for the intermediate ADC values observed in these regions.

Continuous arterial spin labeling perfusion magnetic resonance imaging findings in postpartum vasculopathy.

Postpartum vasculopathy (PPV) is a rare heterogeneous nonatherosclerotic vasculopathy that occurs in the puerperium. It occurs spontaneously but may be triggered by vasoconstrictor substances. The angiographic findings vary and include narrowing of the intracranial arteries and vasospasm. The angiographic findings and the occurrence of ischemic infarcts suggest that cerebral blood flow (CBF) is impaired in PPV. The purpose of this study is to determine CBF in patients with PPV. The authors conducted a case study of 3 patients with clinical and laboratory criteria for PPV examined during a 2-year period. Clinical examination, computed tomography imaging, structural magnetic resonance imaging (MRI), cerebral angiography, and continuous arterial spin labeling perfusion (CASL-PI) MRI were performed in all patients. Mean global CBF was determined, and perfusion maps were visually inspected. The CBF values and perfusion maps were correlated with the clinical symptoms and the neuroimaging findings. Three women were studied (22, 34, and 36 years old). The median time of presentation was 4 days postpartum. One presented with intracranial hemorrhage and diffuse arterial narrowing, the other 2 with stroke-like lesions, encephalopathy, and segmental narrowing mainly in the posterior circulation. CASL-PI was performed within 1 week of symptom onset in all 3 patients. Global mean CBF values were 51.8, 39.3, and 41.8 cc/100 g/min. Although global CBF was mildly diminished, it was above ischemic levels. Visual inspection of the CASL-PI perfusion maps did not reveal areas of focal hypoperfusion or hyperperfusion. In this series of patients with PPV, CBF was close to normal. Although angiography often reveals diffuse arterial narrowing, the CBF values encountered in this study do not support a state of generalized or focal oligoemia. Vasomotor tone may change intermittently in patients with PPV.