F. Gückel

Cerebral blood flow and cerebrovascular reserve capacity: estimation by dynamic magnetic resonance imaging.

We have developed a new method for estimation of regional CBF (rCBF) and cerebrovascular reserve capacity on a pixel-by-pixel basis by means of dynamic magnetic resonance imaging (MRI). Thirteen healthy volunteers, 8 patients with occlusion and/or high grade stenosis of the internal carotid artery (ICA), and 2 patients with acute stroke underwent dynamic susceptibility-weighted contrast enhanced MRI. Using principles of indicator dilution theory and deconvolution analysis, maps of rCBF, regional cerebral blood volume, and of the mean transit time (MTT) were calculated. In patients with ICA occlusion/stenosis, cerebrovascular reserve capacity was assessed by the rCBF increase after acetazolamide stimulation. Mean gray and white matter rCBF values in normals were 67.1 and 23.7 mL · 100 g−1 · min−1, respectively. Before acetazolamide stimulation, six of eight patients with ICA occlusions showed decreased rCBF values; and in seven patients increased MTT values were observed in tissue ipsilateral to the occlusion. After acetazolamide stimulation, decreased cerebrovascular reserve capacity was observed in five of eight patients with ICA occlusion. In acute stroke, rCBF in the central core of ischemia was less than 8 mL · 100 g−1 · min−1. In peri-infarct tissue, rCBF and MTT were higher than in unaffected tissue but rCBF was normal. Dynamic MRI provides important clinical information on the hemodynamic state of brain tissue in patients with occlusive cerebrovascular disease or acute stroke.

Assessment of cerebral blood volume with dynamic susceptibility contrast enhanced gradient-echo imaging

Objective Dynamic susceptibility contrast (DSC) enhanced MRI was used to study relative cerebral blood volume (rCBV). Materials and Methods We examined 15 healthy subjects and 47 patients with vascular stenosis or occlusion, with brain infarctions, and with cerebral neoplasms. During bolus injection of Gd-diethylenetriamine pentaacetic acid, a series of rapid T2*-weighted fast low angle shot two-dimensional images were recorded from the same slice. From these images, changes in signal intensity during bolus passage were computed pixel-by-pixel and converted into contrast agent concentration curves. Applying the principles of indicator dilution theory, images of rCBV were calculated. Results and Conclusion Regions of infarctions show almost zero rCBV. In patients with high-grade vascular stenosis or occlusion a bolus delay in comparison to the unaffected side and an increased mean transit time can be observed. Some of the affected areas show an increased rCBV, which is a well-known physiological mechanism that takes place to compensate for the reduced cerebral blood pressure. In brain tumors, rCBV imaging reveals focal or homogeneous areas of increased blood volume. This can even be observed in low-grade astrocytomas with unaffected blood-brain barrier. In CBV imaging, the effects of radiotherapy on tumor tissue can be monitored as a significant decrease of rCBV in tumor tissue after therapy.

Assessment of Regional Cerebral Blood Volume in Acute Human Stroke by Use of Single-Slice Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

BACKGROUND AND PURPOSE The purpose of this study was to evaluate the clinical usefulness of dynamic susceptibility contrast-enhanced MRI (DSC-MRI) in acute cerebral ischemia. METHODS During bolus injection of gadolinium-diethylenetriamine pentaacetic acid, a series of rapid T2*-weighted images was recorded from one slice. Concentration-time curves and images of regional cerebral blood volume (rCBV) were calculated from this data set. DSC-MRI, MR angiography, conventional spin-echo MRI (SE-MRI), and CT were performed in 11 patients within 6 hours after stroke onset and before thrombolytic or anticoagulant treatment was begun. A follow-up MRI examination was performed 24 to 48 hours after stroke onset. RESULTS In 7 of 11 patients (group 1) with territorial infarcts of the middle (n = 6) or posterior cerebral artery (n = 1), DSC-MRI showed reduced rCBV in the affected territory before conventional SE-MRI displayed ischemic lesions. DSC-MRI was helpful to differentiate severely ischemic tissue from peri-infarct parenchyma. Partial reperfusion (n = 3), unchanged reduction of rCBV (n = 2), and progressive reduction of rCBV (n = 2) were observed in the follow-up study. Normal DSC-MRI findings were present in 4 of 11 patients (group 2) with lacunar infarcts. CONCLUSIONS DSC-MRI accomplished the detection of the ischemic territory in the very early stage (< 6 hours) before SE-MRI delivered unequivocal results. DSC-MRI might be helpful to discriminate completely ischemic tissue from potentially salvageable ischemic parenchyma at risk and may play an important role in stroke therapy and evaluation.

Functional magnetic resonance imaging of category-specific cortical activation: evidence for semantic maps

Functional magnetic resonance imaging (fMRI) was used to examine the pattern of cortical activity during a picture naming task. Subjects (n=12) had to covertly name either animals or furniture items. Functional scanning was performed using a conventional 1.5-Tesla whole-body MRI system. Images obtained during naming the two categories were compared using a non-parametric test. The study revealed evidence for domain-specific lexical regions in left middle, right middle and inferior frontal areas, as well as in superior and middle temporal areas. The results corroborate neuropsychological data and demonstrate directly and non-invasively in human volunteers that semantic representations in frontal and temporal areas are, to some degree, localized and possibly implemented as multiple maps. A completely distributed storage of semantic information is rendered unlikely.

Age dependency of the regional cerebral blood volume (rCBV) measured with dynamic susceptibility contrast MR imaging (DSC)

The changes of the regional cerebral blood volume (rCBV) with age were studied using dynamic susceptibility contrast MRI (DSC). We examined an unselected, random sample of 71 consecutive patients referred for work-up of suspected intracranial tumors (35 normal examinations, 36 tumors) with a standard 1.5 T clinical MR system. Determination of the rCBV was performed with a T2*-weighted simultaneous dual (SD) FLASH sequence (TR/TE1/TE2/alpha = 32/25/16/10 degrees, 55 images) after bolus injection of Gd-DTPA. Absolute quantification of the rCBV was achieved by normalizing the measured tissue concentration-time curves with the integrated arterial input function (AIF), which was simultaneously measured in the brain feeding arteries. The rCBV (mean +/- SD) was 8.4 +/- 2.9 ml/100 g and 4.2 +/- 1.7 ml/100 g in gray and white matter, respectively, with a decline of about 3% and 6% per decade for white and gray matter, respectively. We conclude that DSC using a SD FLASH sequence allows the simultaneous measurement of the AIF and the tissue concentration-time curve and thus an absolute quantification of the rCBV, which is the basis for interperson comparisons and follow-up studies.

Functional MR imaging of the prefrontal cortex: specific activation in a working memory task.

Functional magnetic resonance imaging was used to identify cortical regions activated by a working memory task involving letter detection. Twenty four normal subjects were scanned with a conventional 1.5-T magnet while performing one of two tasks: In the activation task, subjects responded by pressing a button whenever any presented letter was the same as the second last in the sequence. In the control condition, subjects had to respond to a single predefined letter without memory update requirements. The activation task and the control condition were identical with regard to perceptual input and motor output. They were different only regarding the task demand. Movement artifacts were minimized in a two way strategy and eight subjects were excluded from further analysis. Functional MR data from the remaining 16 subjects were analyzed on the basis of anatomical regions-of-interest which were manually defined in each subject. The engagement of working memory produced significant activation in the dorsolateral prefrontal cortex (Brodmanns areas 9, 10, 46, and 47) in both hemispheres. Results demonstrate the applicability of the paradigm within a clinical MRI setup and corroborate previous findings of non-lateralized dorsolateral prefrontal activation during continuous context updating and active maintenance.

Magnetic resonance imaging of bone marrow in lymphoproliferative disorders: correlation with bone marrow biopsy

Summary. In a prospective clinical study 10 normal volunteers and 30 patients with lymphoma—11 patients with Hodgkins lymphoma and 19 patients with non‐Hodgkins lymphoma (11 low grade, 8 high grade)–were examined. Proximal femora, pelvis and lumbar spine were imaged with a 1.5 tesla superconducting MR imaging system (Siemens Magnetom). Areas of malignant infiltration in the bone marrow were clearly detected by visual and/or quantitative assessment. In most cases bone marrow involvement was demonstrated by both magnetic resonance imaging and bone marrow biopsies. However, in three of 30 patients magnetic resonance imaging showed evidence of lymphomatous involvement despite normal bone marrow histology. In one patient bone marrow cytology revealed malignant infiltration in the absence of MRI abnormalities. Thus, MRI is a sensitive method for detecting bone marrow infiltration by lymphoma.

Functional MR imaging of semantic information processing and learning-related effects using psychometrically controlled stimulation paradigms.

Functional magnetic resonance imaging (fMRI), in conjunction with carefully designed, psychometrically optimized stimulation procedures, was used to investigate the relation between brain activation and the processing of word associations. A semantic discrimination task of word-pair similarity was performed by normal subjects (n = 17) within a clinical 1.5-Tesla whole-body MRI system. A color similarity task of psychometrically equivalent difficulty, as indicated by behavioral data acquired online during fMRI, served as active control condition. Comparisons between tasks dramatically improved results compared to comparisons between task and resting condition. The language paradigm selectively activated left frontal and left fronto-temporal areas. Cortical activation during the semantic task decreased significantly over three runs of the same word list and was paralleled by decreased reaction times. No such changes were observed in the active control condition indicating selective learning of the language task only. When combined with psychological activation schemes and the acquisition of behavioral data, fMRI represents a powerful tool for the study of brain-behavior interaction.

Systemic bone marrow disorders: Characterization with proton chemical shift imaging

In a prospective clinical study, 26 patients (22 with malignant lymphoma and 4 with myelofibrosis) and 9 healthy volunteers were examined by conventional magnetic resonance and proton chemical shift imaging (CSI; modified Dixon method). On the basis of the CSI data, a quantitative evaluation of the relative fat and water signal fractions in regions of interest of the femur, pelvis, and spine was performed. In 16 of 17 patients with biopsy-proven bone marrow disorders, CSI revealed a significant reduction in the fat fraction of the bone marrow relative to that of normal volunteers. The visual assessment could detect only 14 of the 17 pathological cases.

Methods for quantitative assessment of tissue microcirculation using dynamic contrast-enhanced MR imaging

SummaryThe development of rapid magnetic resonance imaging (MRI) sequences makes it possible to detect the fast kinetics of tissue response after intraveneous administration of paramagnetic contrast media (CM), reflecting the status of tissue microcirculation. In this paper, the basic physical and tracer kinetic principles of dynamic relaxivity and susceptibility contrast MRI techniques are reviewed. The quantitative analysis of the acquired dynamic image data is broken up into an MR specific part, in which the observed signal variations are related to the CM concentration in the tissue, and an MR independent part, in which the computed concentration-time-courses are analyzed by tracer kinetic modeling. The purpose of the applied models is to describe the underlying physiological processes in mathematical terms and thus to enable the estimation of tissue specific parameters from measured dynamic image series. Whereas the capillary permeability can be estimated from dynamic relaxivity contrast enhanced MRI studies, the regional blood volume as well as the regional blood flow can be determined from dynamic susceptibility contrast enhanced image series. However, since there are no intravascular but only diffusible CM available at present, the application of the susceptibility technique is currently restricted to brain tissues with intact blood brain barrier. The practical realization of both dynamic MRI techniques is demonstrated by case studies.ZusammenfassungDurch die Entwicklung von schnellen MR-Bildgebungssequenzen ist es möglich geworden, die rasche zeitliche Veränderung des Gewebesignals nach intravenöser Applikation eines paramagnetischen Kontrastmittels (KM), die die Mikrozirkulation im Gewebe widerspiegelt, meßtechnisch zu erfassen. In dieser Arbeit werden die physikalischen und tracerkinetischen Grundlagen der relaxations- und suszeptibilitätsgewichteten dynamischen MR-Tomographie (dMRT) vorgestellt. Die quantitative Analyse der gemessenen dynamischen Bilddaten gliedert sich bei beiden Ansätzen in 2 Schritte: einen MR-spezifischen Teil, in dem die gemessene MR-Signalveränderung mit der lokalen KM-Konzentration im Gewebe verknüpft wird, so daß die akquirierten Signal-Zeit-Verläufe in Konzentrations-Zeit-Verläufe umgerechnet werden können, und einen MR-unabhängigen Teil, in dem die Konzentrations-Zeit-Verläufe mittels geeigneter tracerkinetischer Modelle analysiert werden. Durch die Modellbildung wird physiologisches und histologisches Vorwissen bezüglich der Mikrozirkulation im Gewebe mathematisch formuliert, so daß relevante Gewebeparameter quantitativ aus den dynamischen Bildserien berechnet werden können. So bietet die relaxationsgewichtete dMRT die Möglichkeit, die Permeabilität der Blutgefäße in der terminalen Strombahn zu beurteilen, während mit der suszeptibilitätsgewichteten dMRT das regionale Blutvolumen und der regionale Blutfluß bestimmt werden kann. Da bislang noch keine intravasalen sondern nur diffusible MR-KM für klinische Studien zugelassen sind, ist die Anwendung der suszeptibilitätsgewichteten dMRT derzeit allerdings auf Hirngewebe mit intakter Blut-Hirn-Schranke eingeschränkt. Die praktische Anwendung der beiden dMRT-Techniken wird jeweils an einem klinischen Fallbeispiel erläutert.