Perfusion and diffusion MR imaging of thromboembolic stroke

A carotid embolic stroke model in rats was studied with a combination of diffusion- and perfusion-sensitive magnetic resonance (MR) imaging at 4.7 T. Capillary blood deoxygenation changes were monitored during formation of focal ischemia by acquiring multisection magnetic susceptibility-weighted echo-planar images. A signal intensity decrease of 7% ± 3 in ischemic brain (1% ± 2 in normal brain) was attributable to a T2* decrease due to increased blood deoxygenation, which correlated well with subsequently measured decreases in the apparent diffusion coefficient. The same multisection methods were used to track the first-pass transit of a bolus of dysprosium-DTPA-BMA [diethylenetriaminepentaacetic acid-bis(methylam-ide)] to assess relative tissue perfusion before and after stroke and after treatment with a thrombolytic agent. Analysis of contrast agent transit profiles suggested a total perfusion deficit in ischemic tissue and essentially unchanged perfusion in normal brain tissue after stroke.     

Selective enhancement of experimental rat brain tumors with Gd-TPPS

The synthetic metalloporphyrin gadolinium (III)-tetraphenylporphine sulfonate (TPPS) was successfully used as a contrast agent for in vivo magnetic resonance (MR) imaging of rat brain glioma. After injection of Gd-TPPS, the signal intensity of experimental rat brain glioma distinctly increased on T1-weighted MR images, an effect similar to that produced by the clinically applied MR imaging contrast agent gadolinium diethylenetriaminepentaacetic acid (DTPA). In contrast to other contrast agents studied (Gd-DTPA, manganese [III]-TPPS), Gd-TPPS produced hypointensity in glioma on T2-weighted images. The tumor-selective accumulation of paramagnetic Gd-TPPS in glioma shortened T1 by 53%, from 1,315 msec ± 199 to 628 msec ± 106, and T2 by 34%, from 86 msec ± 4 to 57 msec ± 5 (2 days after injection of 0.25 mmol/kg Gd-TPPS). The relaxation times of normal cortex, striaturn, corpus callosum, and temporal muscle were not significantly affected. As a result, gliomas appeared hyperintense on T1-weighted images and hypointense on T2-weighted images. Owing to the strong effect of Gd-TPPS on the T2 of glioma, normal brain tissue, tumor, and peritumorous edema could be distinguished on T2-weighted images alone.     

Comparison of T2-weighted spin-echo and fast spin-echo techniques in the evaluation of myelination

To evaluate T2-weighted fast spin-echo (FSE) and conventional spin-echo (CSE) magnetic resonance (MR) techniques in the assessment of brain myelination, 100 consecutive pediatric patients were imaged prospectively with both CSE and FSE sequences. All patients underwent a routine MR examination that included T2-weighted CSE imaging (imaging time, 10 minutes 21 seconds) and T2-weighted FSE imaging (imaging time, 2 minutes 5 seconds). The two techniques were compared for estimating the degree of myelination (using normal anatomic landmarks) by blind review. With T2-weighted CSE images as the “gold standard” for estimation of normal myelination, FSE images were evaluated to determine if they showed the degree of myelination similarly to CSE images. There was a strong correlation (P <.01) between CSE and FSE images in the estimation of myelination over a wide range of patient ages.     

Cerebral blood flow: assessment with dynamic contrast-enhanced T2*-weighted MR imaging at 1.5 T

The authors assessed regional cerebral blood flow dynamics with magnetic resonance (MR) imaging enhanced with gadolinium diethylenetriaminepentaacetic acid (DTPA). After bolus administration of Gd-DTPA, rapid T2*-weighted gradient-echo images were acquired. Image acquisition time ranged from 2 to 3 seconds. The signal intensity (SI) of brain tissue and blood vessels markedly decreased during the first pass of contrast agent through the brain due to the local field inhomogeneity caused by the concentrated paramagnetic contrast agent. The method was used in 18 subjects with no cerebrovascular disease and 32 patients with stroke, vascular stenosis, arteriovenous malformation, and cerebral neoplasm. Comparison with intracranial angiography was performed in three patients and with single-photon emission computed tomography of blood flow in four. The change in T2* relaxation rate was approximately linearly related to the dose of contrast agent. The SI change increased as the echo time was lengthened. Regions in cerebral infarcts, metastases, and arteriovenous malformations showed different enhancement patterns than those of edema around a lesion and of normal brain tissue. Abnormal circulation times in patients with vascular stenoses were demonstrated. The method provides information about cerebral blood flow dynamics not available from conventional MR imaging and MR angiography.     

Echo-planar MR imaging of human brain oxygenation changes

Echo-planar magnetic resonance (MR) imaging was used to observe signal intensity changes in the human brain during hypoxia. Increasing arterial blood levels of deoxyhemoglobin (0%–42%) during prolonged apnea were monitored with a pulse oximeter and correlated with gray matter and white matter signal attenuation of 13% and 20%, respectively. The results suggest the possibility of using deoxyhemoglobin boluses as a physiologic, intravascular susceptibility contrast agent for assessment of local cerebral oxygen utilization.     

Perfusion-weighted MRI using gadobutrol as a contrast agent in a rat stroke model

The purpose of this study was to examine the new nonionic contrast agent gadobutrol in MR perfusion-weighted imaging, including the influence of different concentrations and dosages of the agent on the sensitivity to perfusion alterations. Sixteen rats were examined within 35 to 105 minutes after endovascular occlusion of the middle cerebral artery. A fast T2*-weighted fast low-angle shot (FLASH) sequence was used to acquire four images before and 16 images after bolus injection of .1, .2, .3, and .4 mmol/kg gadobutrol as .5 molar and 1.0 molar formulation. From user-defined regions, we obtained the maximum signal decrease, the relative regional cerebral blood volume, and the bolus delay. Contrast between ischemic and nonischemic regions during bolus passage increased with dose and concentration of the contrast agent. For low doses (.1 and .2 mmol/kg), the ischemic lesion could not or could barely be discerned. For higher doses (.3 and .4 mmol/kg), administration of the 1 molar contrast agent yielded a better contrast between ischemic and nonischemic tissue. Our results suggest that administration of gadobutrol at higher dosage and higher concentration increases sensitivity to perfusion alterations. These results are potentially useful for perfusion-weighted imaging of the human brain, because the volume of contrast agent will be reduced if a solution with higher concentration is used. When using contrast agents in higher concentrations for human examinations, a significant signal decrease may be achieved also with the low doses (.1–.15 mmol/kg).     

First pass of an MR susceptibility contrast agent through normal and ischemic heart: Gradient-recalled echo-planar imaging

Gradient-recalled echo-planar magnetic resonance (MR) imaging was used to monitor the first pass of a magnetic susceptibility contrast agent through the heart of normal rats and rats subjected to 60-minute occlusion of the anterior branch of the left main coronary artery. Each animal (six normal and six ischemic) received four doses (0.05, 0.1, 0.15, and 0.2 mmol/kg) of Dy-DTPA-BMA [diethylenetriaminepentaacetic acid–bis(methylamide)] administered as a bolus volume of 1.0 mL/kg. In both normal and ischemic rats, signal intensity in nonischemic myocardium was reduced by the contrast agent in a dose-dependent manner. Signal intensity in the ischemic zone was reduced much less, so that at a contrast agent dose of 0.1 mmol/kg or greater the ischemic zone was clearly defined as a high-intensity zone on echo-planar images. Plots of the change in the apparent T2* relaxation rate (ΔR2*) during the peak bolus effect versus injected dose were well fit by straight lines for normal, nonischemic, and ischemic myocardium but not for blood in the left ventricle. No difference was seen between myocardial response in normal animals and in nonischemic regions in animals with coronary artery occlusion. These findings suggest that the contrast agent–induced changes in tissue T2* are monoexponential and support the idea that data derived from contrast transit studies may be useful for calculation of myocardial blood flow.     

Preliminary clinical trial of gadodiamide injection: a new nonionic gadolinium contrast agent for MR imaging.

The safety and efficacy of a newly developed intravenous formulation of the nonionic contrast agent gadolinium diethylenetriaminepentaacetic acid-bis(methylamide), formulated as gadodiamide injection, was investigated. In 30 patients who underwent spin-echo magnetic resonance (MR) imaging before and after contrast agent enhancement, the enhanced images had characteristics judged similar to those of images enhanced by means of available gadolinium compounds. In 15 patients, contrast agent administration was of major diagnostic help, either revealing lesions not apparent without enhancement or providing important lesion characterization. In 12 patients, the lack of abnormal enhancement patterns was important in excluding the presence of disease. In three patients, the contrast agent did not provide information additional to that obtained with the unenhanced T1- and T2-weighted images. No clinically significant changes were observed in vital signs, neurologic status, or laboratory results. The authors conclude that, in this limited series, gadodiamide injection proved to be a safe and useful MR imaging contrast agent for evaluation of the central nervous system and surrounding structures.     

Diffusion-weighted MR imaging of acute stroke: correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats

We evaluated the temporal and anatomic relationships between changes in diffusion-weighted MR image signal intensity, induced by unilateral occlusion of the middle cerebral artery in cats, and tissue perfusion deficits observed in the same animals on T2-weighted MR images after administration of a nonionic intravascular T2 shortening agent. Diffusion-weighted images obtained with strong diffusion-sensitizing gradient strengths (5.6 gauss/cm, corresponding to gradient attenuation factor, b, values of 1413 sec/mm2) displayed increased signal intensity in the ischemic middle cerebral artery territory less than 1 hr after occlusion, whereas T2-weighted images without contrast usually failed to detect injury for 2-3 hr after stroke. After contrast administration (0.5-1.0 mmol/kg by Dy-DTPA-BMA, IV), however, T2-weighted images revealed perfusion deficits (relative hyperintensity) within 1 hr after middle cerebral artery occlusion that corresponded closely to the anatomic regions of ischemic injury shown on diffusion-weighted MR images. Close correlations were also found between early increases in diffusion-weighted MR image signal intensity and disrupted phosphorus-31 and proton metabolite levels evaluated with surface coil MR spectroscopy, as well as with postmortem histopathology. These data indicate that diffusion-weighted MR images more accurately reflect early-onset pathophysiologic changes induced by acute cerebral ischemia than do T2-weighted spin-echo images.     

Detection with echo-planar MR imaging of transit of susceptibility contrast medium in a rat model of regional brain ischemia.

Gradient-refocused echo-planar magnetic resonance (MR) images (TE = 18 msec) were acquired in rats during bolus injection of iron oxide particles, and the first pass of the contrast agent through the brain was monitored. In control rats, contrast agent (0.1 mmol/kg iron) produced significant signal-intensity (SI) reduction over the right hemisphere and similar declines over the left. SI loss occurred first in the cortex and basal ganglia and later in the periventricular regions, along the midline, and in the thalamic zone. Sequential volume-localized proton spectra acquired during transit of 0.02 mmol/kg iron showed substantial reduction in SI, slight asymmetric broadening, and no change in chemical shift of the water resonance. In rats with unilateral occlusion of the middle cerebral artery, peak reduction in ischemic brain SI was to 70% +/- 9% of control, while normal brain SI was reduced to 18% +/- 2% (P less than .01), allowing distinction of the ischemic regions. The presence and location of injury were confirmed with diffusion-weighted imaging and postmortem vital staining. These results demonstrate abnormal transit profiles in a rat model of regional brain ischemia. Evaluation of dynamic contrast delivery patterns may provide unique information in early brain ischemia.     

Dynamic contrast-enhanced T2*-weighted MR imaging of tumefactive demyelinating lesions.

PURPOSE: Dynamic contrast-enhanced T2*-weighted MR imaging has been helpful in characterizing intracranial mass lesions by providing information on vascularity. Tumefactive demyelinating lesions (TDLs) can mimic intracranial neoplasms on conventional MR images, can be difficult to diagnose, and often result in surgical biopsy for suspected tumor. The purpose of this study was to determine whether dynamic contrast-enhanced T2*-weighted MR imaging can be used to distinguish between TDLs and intracranial neoplasms that share common features on conventional MR images. METHODS: We retrospectively reviewed the conventional and dynamic contrast-enhanced T2*-weighted MR images and medical records of 10 patients with tumefactive demyelinating disease that was diagnosed by either biopsy or strong clinical suspicion supported by laboratory evaluation that included CSF analysis and evoked potential tests. Twelve TDLs in 10 patients and 11 brain tumors that appeared similar on conventional MR images were studied. Relative cerebral blood volume (rCBV) was calculated from dynamic MR data and was expressed as a ratio to contralateral normal white matter. rCBV values from 11 patients with intracranial neoplasms with very similar conventional MR imaging features were used for comparison. RESULTS: The rCBV values of TDLs ranged from 0.22 to 1.79 (n = 12), with a mean of 0.88 +/- 0.46 (SD). The rCBV values of intracranial neoplasms ranged from 1.55 to 19.20 (n = 11), with a mean of 6.47 +/- 6.52. The difference in rCBV values between the two groups was statistically significant (P =.009). The difference in rCBV values between TDLs and primary cerebral lymphomas (n = 4) was less pronounced but was statistically significant (P =.005). CONCLUSION: Dynamic contrast-enhanced T2*-weighted MR imaging is a useful diagnostic tool in differentiating TDLs from intracranial neoplasms and may therefore obviate unnecessary surgical biopsy.     

Brain MR Imaging in dietarily treated phenylketonuria

Magnetic resonance imaging is the most efficient imaging modality to evaluate brain gray and white matter of patients with metabolic diseases [1, 2, 3]. The main purpose of out study was to investigate the relation between brain MRI abnormalities and the phenylalanine (phe) and tyrosine (tyr) blood levels in 38 phenylketonuria (PKU) patients. Increased periventricular white matter intensity on T2-weighted brain images was the only pahtologic finding in 24 patients. Brain MRI abnormalities were scored (4) and correlated with the individual mean phe and phe/ tyr levels during 1 year preceding MR examination and with phe tolerance. The appearance of MRI abnormalities on brain T2-weighted images correlates with a threshold mean phe level (averaged over the year preceding the examination).     

Significance of the perfusion-diffusion mismatch in chronic cerebral ischemia

PURPOSE: To determine whether the perfusion deficit could predict brain infarction in patients with chronic cerebral ischemia who experienced recurring episodes of neurological symptoms and showed a perfusion-diffusion mismatch on magnetic resonance (MR) images. MATERIALS AND METHODS: In 53 consecutive patients (38 males and 15 females, 62+/-13 years old) with ischemia in the middle cerebral artery (MCA) territory, lesion volumetry was performed on parametric maps of the time-to-peak, the cerebral blood volume, and diffusion-weighted (DW) images. The infarct lesions were assessed on follow-up T2-weighted (T2W) MR images after eight days. Cerebrovascular changes were determined by time-of-flight (TOF) MR angiography (MRA). Inferential and correlation statistics were used. RESULTS: Patients with chronic ischemic brain disease (N=39) who presented with a severe perfusion-diffusion mismatch in the presence of a normal cerebral blood volume had no or small brain infarctions as found on follow-up T2W images. MRA revealed widespread abnormalities of the basal cerebral arteries compatible with brain perfusion abnormalities. In contrast, in acute stroke patients (N=14) the deficit of cerebral perfusion predicted the infarct lesion in the T2W images. CONCLUSION: Our results suggest that in chronic cerebral ischemia the normal blood volume was maintained despite the depression of cerebral perfusion and recurring minor insults.     

MR imaging of cerebral ischemia: findings in the first 24 hours.

MR changes of cerebral ischemia have been shown to occur as early as 1-2 hr after vessel occlusion in experimental models of stroke. However, the MR findings in the early stages of ischemic stroke in the clinical population have not been well established. We studied 41 lesions in 39 patients in whom MR was performed within the first 24 hr after onset of ischemic symptoms. Twenty-five lesions were studied with gadopentetate dimeglumine. Vascular flow-related abnormalities, including absence of normal flow void and presence of arterial enhancement, were the earliest MR findings, detected within minutes of onset. Morphologic changes (brain swelling) on T1-weighted images without signal changes on T2-weighted images could be detected within the first few hours. Signal changes were not usually found before 8 hr on T2-weighted images or before 16 hr on T1-weighted images. In contrast to the absence of parenchymal enhancement typically found in cortical infarctions in the first 24 hr, a few lesions (including transient occlusions, partial occlusions, and isolated watershed infarctions) exhibited early, exaggerated parenchymal enhancement. We conclude that signal changes may not be reliable in detecting ischemic stroke within the first 8 hr after onset. Vascular abnormalities, when present, are the most reliable and earliest findings. Other MR findings of early ischemic stroke, including morphologic changes and early, exaggerated parenchymal enhancement, may also precede signal changes. Paramagnetic contrast administration often provides valuable information in the detection and evaluation of acute ischemia.     

Early detection of regional cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy

Diffusion-weighted MR images were compared with T2-weighted MR images and correlated with 1H spin-echo and 31P MR spectroscopy for 6-8 h following a unilateral middle cerebral and bilateral carotid artery occlusion in eight cats. Diffusion-weighted images using strong gradient strengths (b values of 1413 s/mm2) displayed a significant relative hyperintensity in ischemic regions as early as 45 min after onset of ischemia whereas T2-weighted spin-echo images failed to clearly demonstrate brain injury up to 2-3 h postocclusion. Signal intensity ratios (SIR) of ischemic to normal tissues were greater in the diffusion-weighted images at all times than in either TE 80 or TE 160 ms T2-weighted MR images. Diffusion- and T2-weighted SIR did not correlate for the first 1-2 h postocclusion. Good correlation was found between diffusion-weighted SIR and ischemic disturbances of energy metabolism as detected by 31P and 1H MR spectroscopy. Diffusion-weighted hyperintensity in ischemic tissues may be temperature-related, due to rapid accumulation of diffusion-restricted water in the intracellular space (cytotoxic edema) resulting from the breakdown of the transmembrane pump and/or to microscopic brain pulsations.     

Determinants of signal intensity in MRI of human astrocytomas

MRI studies at 1.5 T of 38 patients with histologically confirmed astrocytomas were reviewed to search for a relationship of signal intensity with grade of malignancy, rediotherapy used for recurrent tumours and calcium deposits in surgical specimens. Signal intensity of tumours compared with normal brain was rated on a scale of 1 to 5 on T1- and T2-weighted images. Surgical specimens of each tumour were graded histopathologically on a scale of I to III and examined for calcium deposits. CT scans were searched for evidence of calcification. The majority of astrocytomas appeared hypointense on T1-weighted and hyperintense on T2-weighted images. Of 18 tumours with increased signal on T1-weighted images, grade II were prevalent, followed by calcified astrocytomas. Among 14 tumours with decreased signal on T2-weighted images the order was similar, but the ratio of high-grade to low-grade tumours did not differ in relation to signal intensity, while on T1-weighted images the ratio was higher in the group with increased signal intensity. A high grade of malignancy and microcalcifications were associated with an increased signal intensity of astrocytomas on T1-weighted sequences without contrast agent. The above factors did not influence significantly the signal intensity on T2-weighted images. Correspondence to: B. Góraj     

Comparison of CT and three MR sequences for detecting and categorizing early (48 hours) hemorrhagic transformation in hyperacute ischemic stroke

BACKGROUND AND PURPOSE: Our goal was to compare the sensitivity of CT and three MR sequences in detecting and categorizing early (48 hours) hemorrhagic transformation (HT) in hyperacute ischemic stroke. METHODS: Twenty-five consecutive patients with hyperacute ischemic stroke (<6 hours) without MR signs of cerebral bleeding at admission were included. Twenty-one underwent thrombolytic therapy. A standardized follow-up protocol, performed 48 hours after admission, combined brain CT scan and MR examination (1.5 T) including fast spin-echo-fluid-attenuated inversion recovery (FSE-FLAIR), echo-planar spin-echo (EPI-SE) T2-weighted, and EPI-gradient-recalled echo (GRE) T2*-weighted sequences. Both CT scans and MR images were obtained within as short a time span as possible between techniques (mean delay, 64 minutes). CT scans and MR images were independently rated as negative or positive for bleeding and categorized for bleeding severity (five classes) by two blinded observers. Prevalence of positive cases, intra- and interobserver agreement, and shifts in bleeding categorization between respective modalities and sequences were assessed. RESULTS: Twelve patients (48%) were rated positive for HT on the basis of findings of at least one technique or sequence. From this subset of bleeding patients, seven (58%) had positive CT findings, nine (75%) had positive FSE-FLAIR and EPI-SE T2-weighted findings, and 12 (100%) had positive EPI-GRE T2*-weighted findings. CT had lower intra- and interobserver agreement for positivity than did MR imaging. Among the seven patients with positive CT and MR findings, only two had convergent ratings for bleeding category based on findings of two modalities. The five remaining had upward grading from CT to MR, which varied according to pulse sequence. CONCLUSION: MR imaging depicted more hemorrhages and had higher intra- and interobserver agreement than did CT. The EPI-GRE T2*-weighted sequence demonstrated highest sensitivity. Equivocal upward shifts in bleeding categorization were observed from CT to MR imaging and between MR images.     

Early radiation effects on the liver demonstrated on superparamegnetic iron oxide-enhanced T1-weighted MRI

Early radiation-induced liver injury during radiotherapy detected by a particulate reticuloendothelial MR contrast agent (superparamagnetic iron oxide; SPIO) is described in a patient with cholangiocarcinoma. The irradiated hepatic parenchyma appeared as a heterogeneous, less decreased signal intensity area than the nonirradiated area on MR images after SPIO administration. Resultant differences in signal intensity were better visualized on SPIO-enhanced T1-weighted images than SPIO-enhanced T2-weighted images, although SPIO-enhanced T2*-weighted fast field echo imaging was the most sensitive.     

Contrast-enhanced T1-weighted black-blood fast spin-echo MR imaging of the brain. Technique for suppression of enhancing venous signal

Purpose: Contrast-enhanced T1-weighted black-blood fast spin-echo MR imaging (BB-FSE) was performed to suppress enhancing venous signal and flow artifacts in the brain without sacrificing the T1-weighted imaging contrast.Material and Methods: Twenty-five MR imaging sections (17 transverse and 8 coronal images) in 15 patients with various brain diseases were obtained by contrast-enhanced T1-weighted SE and BB-FSE images.Results: In contrast-enhanced T1-weighted BB-FSE images, venous signal was significantly less and T1-weighted contrast of the brain was more evident. No differences in flow artifacts were found between the two imaging techniques. The interobserver agreements were good for the venous signal and flow artifacts using both techniques.Conclusion: Contrast-enhanced T1-weighted BB-FSE imaging reduced the venous signal in the brain with maintaining T1-weighted contrast. This novel MR technique can be used when the suppression of enhancing venous signal is expected to improve the depiction of enhancing lesions in the brain.     

Dual dynamic contrast-enhanced MR imaging

A method was devised for obtaining dynamic contrast-enhanced T1-weighted and relaxation rate (ΔR2*) images simultaneously to evaluate regional hemodyn-amics of the brain tumors. On a 1.5-T MR system, dual dynamic contrast-enhanced images were obtained using a gradient echo (dual echo fast field echo) pulse sequence with the keyhole technique to improve temporal and spatial resolution during a rapid bolus injection of gadopentetate dimeglumine. The dynamic T1 contrast images were obtained from the first echo; moreover. ∫ ΔR2*dt values were calculated from the first and the second echo images. The dynamic T1 contrast images provided information about characteristic enhancement pattern (vascularization and disruption of bloodbrain barrier), and the f ΔR2*dt values provided a map of regional blood pool in tumor site, peritumoral edema, and other surrounding regions of the brain. The ability to obtain dynamic contrast-enhanced T1 contrast and ΔR2* imaging at the same time allows optimization of the advantages of each and thereby more information about the microvascular circulation of the brain lesions.