Quantitative Cerebral Blood Flow Research Articles

Qualitative versus quantitative assessment of cerebrovascular reserves.

Quantitative studies of cerebral blood flow (CBF) combined with a vasodilatory challenge have defined a subgroup of patients with symptomatic carotid occlusion who have an increased risk for stroke. These are patients whose CBF paradoxically decreases in response to a vasodilatory challenge. Recent reports suggest that qualitative CBF techniques, such as single photon emission tomography with 99m-hexamethylpropyleneamine oxime, can also define the same high-risk subgroup. To determine whether qualitative measures of CBF are sufficient for predicting the risk of stroke, we converted our quantitative CBF data, obtained with xenon-enhanced computed tomography (Xe/CT), to qualitative ratios in a manner similar to that used with single photon emission tomography data. We analyzed CBF values within the territory of the middle cerebral artery for 94 patients with symptomatic carotid occlusion. Values obtained using Xe/CT before and after the intravenous administration of 1 g of acetazolamide were used to derive an asymmetry index: (Coccl - Cnon)/Cavg x 100. The difference between the postacetazolamide asymmetry index and the baseline asymmetry index was used to classify the patients into groups according to CBF values. The threshold for abnormal qualitative CBF reactivity was defined as a percent change in the asymmetry index of less than -10%. Quantitative (Xe/CT) CBF was considered abnormal ("steal" response) when the response to acetazolamide (percent change) on the occluded side was a decrease of 5% or greater. Of 34 patients whose cerebrovascular reserves were considered compromised based on qualitative criteria, 17 (50%) did not have a steal response as defined by quantitative Xe/CT CBF (i.e., false positive). Eleven of 62 (18%) who were not considered compromised by qualitative criteria had a steal response (i.e., false negative). Our data indicate that a qualitative approach has a 61% sensitivity and a 75% specificity for detecting patients with compromised reserves. Further, the positive predictive value of this method is only 50%. Therefore, the two methodologies do not predict the same patients as having compromised reserves. Previous studies have shown that patients at high risk for stroke can be identified with quantitative CBF methods. This study shows that the important subgroup cannot be accurately defined with qualitative methodology. The implications of using the more reliable methodology are important for individual patient management and for designing clinical trials.

Multislice imaging of quantitative cerebral perfusion with pulsed arterial spin labeling.

A method is presented for multislice measurements of quantitative cerebral perfusion based on magnetic labeling of arterial spins. The method combines a pulsed arterial inversion, known as the FAIR (Flow-sensitive Alternating Inversion Recovery) experiment, with a fast spiral scan image acquisition. The short duration (22 ms) of the spiral data collection allows simultaneous measurement of up to 10 slices per labeling period, thus dramatically increasing efficiency compared to current single slice acquisition protocols. Investigation of labeling efficiency, suppression of unwanted signals from stationary as well as intraarterial spins, and the FAIR signal change as a function of inversion delay are presented. The assessment of quantitative cerebral blood flow (CBF) with the new technique is demonstrated and shown to require measurement of arterial transit time as well as suppression of intraarterial spin signals. CBF values measured on normal volunteers are consistent with results obtained from H2O15 positron emission tomography (PET) studies and other radioactive tracer approaches. In addition, the new method allows detection of activation-related perfusion changes in a finger-tapping experiment, with locations of activation corresponding well to those observed with blood oxygen level dependent (BOLD) fMRI.

Multislice Imaging of Quantitative Cerebral Perfusion with Pulsed Arterial Spin-Labeling

A method is presented for multislice measurements of quantitative cerebral perfusion based on magnetic labeling of arterial spins. The method combines a pulsed arterial inversion, known as the FAIR (Flow-sensitive Alternating Inversion Recovery) experiment, with a fast spiral scan image acquisition. The short duration (22 ms) of the spiral data collection allows simultaneous measurement of up to 10 slices per labeling period, thus dramatically increasing efficiency compared to current single slice acquisition protocols. Investigation of labeling efficiency, suppression of unwanted signals from stationary as well as intraarterial spins, and the FAIR signal change as a function of inversion delay are presented. The assessment of quantitative cerebral blood flow (CBF) with the new technique is demonstrated and shown to require measurement of arterial transit time as well as suppression of intraarterial spin signals. CBF values measured on normal volunteers are consistent with results obtained from H2O15 positron emission tomography (PET) studies and other radioactive tracer approaches. In addition, the new method allows detection of activation-related perfusion changes in a finger-tapping experiment, with locations of activation corresponding well to those observed with blood oxygen level dependent (BOLD) fMRI.

Quantitative Cerebral Blood Flow Determinations in Acute Ischemic Stroke

The advent of new modalities to treat acute ischemic stroke presents the need for accurate, early diagnosis. In acute ischemic stroke, CT scans are frequently normal or reveal only subtle hypodense changes. This study explored the utility and increased sensitivity of xenonenhanced CT (XeCT) in the diagnosis of acute cerebral ischemia and investigated the relationship between cerebral blood flow (CBF) measurements and early CT and angiographic findings in acute stroke. The CT scans, XeCT scans, and angiograms of 20 patients who presented within 6 hours of acute anterior circulation ischemic strokes were analyzed. CT scans were abnormal in 11 (55%) of 20 patients. XeCT scans were abnormal in all 20 (100%) patients, showing regions of interest with CBF < 20 (mL/100 g per minute) in the symptomatic middle cerebral artery (MCA) territories. The mean CBF in the symptomatic MCA territories was significantly lower than than of the asymptomatic MCA territories (P < .0005). In patients with basal ganglia hypodensities, the mean symptomatic MCA territory CBF was significantly lower than that of patients who did not exhibit these early CT findings (P < .05). The mean symptomatic MCA territory CBF in patients with angiographic M1 occlusions was significantly lower than that of patients whose infarcts were caused by MCA branch occlusions (P < .01). These results show that XeCT is more sensitive than CT in detecting acute strokes and that CBF measurements correlate with early CT and angiographic findings. XeCT may allow for the hyperacute identification of subsets of patients with acute ischemic events who are less likely to benefit and more likely to derive complications from aggressive stroke therapy.

Quantitative cerebral blood flow and metabolism determination in the first 48 hours after severe head injury with a new dynamic SPECT device.

To determine cerebral blood flow (CBF) and metabolism in the acute phase after severe head injury by a new dynamic SPECT device using 133Xenon and to evaluate a possible role of CBF and metabolism in the determination of prognosis. Prospective study. General intensive care unit in a universitary teaching hospital. 23 severely head injured patients having CT scan and CBF determination, intracranial pressure (ICP) and jugular bulb oxygen saturation monitoring in the first 48 hours. CBF varied from 18.0 to 60.0 ml/100 g/min. No correlation was found between early CBF and severity of trauma evaluated with the Glasgow Coma Score (GCS) (F = 2.151, p = 0.142) and between CBF and prognosis at 6 months evaluated with Glasgow outcome score (GOS) (F = 0.491, p = 0.622: rs = 0.251, p = 0.246). CMRO2 was depressed in relation to the severity of injury, specifically ranging from 0.9 +/- 0.5 ml/100 g/min in patients with GCS 3 to 1.7 +/- 0.8 ml/100 g/min in patients with GCS 6-7. In no patient with CMRO2 less than 0.8 ml/100 g/min was a good outcome observed. A significant correlation was found between GCS and GOS (rs = 0.699, p = 0.0002), between CMRO2 and GOS (F = 4.303, p = 0.031; rs = 0.525, p = 0.013) and between AJDO2 and GOS (F = 3.602, p = 0.046; rs = 0.491, p = 0.017). Fronto-occipital ratio (F/O) of CBF distribution was significantly lower than normal values (chi 2 = 18.658, p = 0.001) but did not correlate either with prognosis (chi 2 = 1.626, p = 0.443) or with severity (chi 2 = 1.913, p = 0.384). CBF in the first 48 hours after trauma varies within a large range of values and is not correlated with severity and prognosis. Clinical evaluation with GCS and CMRO2 are much more reliable indicators of severity of head trauma and have a significant role in the determination of prognosis. F/O ration is significantly altered from normal values confirming "post-traumatic hypofrontalism" but does not correlate with severity and prognosis.

Lateralized Changes in Regional Cerebral Blood Flow during Performance of Verbal and Facial Recognition Tasks: Correlations with Performance and “Effort”

Functional neuroimaging has been used to investigate neural substrates of mnemonic processes, and cerebral blood flow (CBF) measures have been sensitive to activation with memory tasks. Studies of memory with two-dimensional133Xenon clearance techniques found that word and face recognition tasks produced contralateral CBF changes in mid-temporal cortical regions. This study replicated the activation paradigm, expanding to the three-dimensional resolution of positron emission tomography (PET). Word and face recognition, and a control baseline task were administered to 19 healthy right-handed volunteers (11 men, 8 women) during successive 10 min PET15O-water measures of CBF. Quantitative CBF rates were calculated with the arterial input function and the equilibrium model. Redistributions of blood flow were compared across tasks using both absolute and relative (region/whole brain) CBF.Replicating the133Xenon clearance findings, CBF was “appropriately” lateralized during task performance (left–right for words > left–right for faces) in the mid-temporal region. Contrary to predictions, the recognition tasks did not activate expected mesolimbic or prefrontal areas. The task-induced CBF changes also correlated with performance. Bilateral CBF in mid-temporal and parahippocampal gyrus regions of interest correlated with the ability to correctly identify word targets (sensitivity). Left-lateralized CBF in the amygdala and hippocampus correlated with better word sensitivity as well as specificity (ability to correctly reject foils). Complementally, right-lateralized CBF in the parahippocampal gyrus correlated with better face specificity performance. In addition, left-lateralized CBF in the amygdala and right-lateralized CBF in the parahippocampal gyrus and hippocampus correlated with “mental effort” indices (task performance relative to basal ability) for word and face memory tasks, respectively. Thus, whereas this recognition task showed the expected lateralized increase in the mid-temporal region and not in frontal and limbic areas, lateralized activation in some of these areas was associated with better performance. Exploratory analyses on other regions showed lateralized changes in one additional temporal region, the occipital-temporal, and several limbic regions.

Xenon/Computed Tomography Cerebral Blood Flow and its use in Clinical Management

The main advantages of stable Xe/CT is that it noninvasively provides rapid access to high-resolution, quantitative, local CBF information coupled to CT anatomy. The information obtained is valid even in disease states because a partition coefficient is directly calculated for each voxel as small as 1 x 1 x 5 mm3. CBF studies can be repeated within 20 minutes, allowing the assessment of hemodynamic states. The technology can be incorporated into all existing CT technology at relatively little expense. The disadvantages are the radiation dose from the CT scanner, the pharmacologic effects of xenon gas, and the limitations of survey. The radiation dose is significant but it is focused to the least radiation-sensitive region of the body (scalp, skull, and brain) so that the effective cancer causation risk is lower than any other CBF study that delivers isotope indescriminatly to the body. The pharmacologic properties of xenon are associated with several potential problems. Xenon alters the sensorium of many individuals and may cause patient motion. This can be minimized with careful prestudy positioning and reassurance of the patient during the study. Most patients find the sensation enjoyable; however, occasionally, a patient cannot tolerate the perception of "losing control" and the study has to be stopped. One of the concerns regarding Xe/CT is that at the 80% level, xenon has anesthetic properties. At less than 33% xenon (with the difference being oxygen), the side effects have, in fact, been few and transient, with a mild hyperesthetic and disassociated feeling being the rule. Although xenon-induced apnea was reported as a consequence of xenon inhalation, the report involved the inhalation of 100% xenon, and at the levels recommended for imaging, holding one's breath for more than 20 seconds is rare. The other concern is the degree of flow activation that occurs with xenon inhalation and its effect on the accuracy of the measurements. In part, because of the "robust" nature of the Kety-Schmidt equations and because a significant xenon-induced flow activation is delayed for about 2 minutes, the effect of the flow activation is, in fact, minimal (less than 5% elevation of calculated flow values from true values). Although an earlier study by Obrist36 suggested that the error induced by flow activation was significant, a recent computer simulation study by the same author identified a maximal theoretical error of less than 5%. Previously, Xe/CT studies were limited to three brain levels, but with the new helical CT scanners, nine levels can now be studied. Most of the concerns over the technology have been resolved (Table 1). As a result, more clinicians around the world are beginning to use this technology when they need rapid access to quantitative CBF information about their patients.

33. Quantitative cerebral blood flow analysis in predicting radiosurgical outcome in cerebral AVM

Kashyap, R.; Carroll, M. J.; Huneidi, A. H.S.; Nimmon, C.; Plowman, P. N.; Britton, K. E. Author Information

Perfusion imaging with compensation for asymmetric magnetization transfer effects

The effects of off-resonance radio-frequency irradiation on the intensity of the MR signal from water protons in the cat brain are asymmetric around the chemical shift of the water signal. This asymmetry, which could arise from a shift in the magnetization transfer spectrum approximately 1.5 ppm upfield from the solvent water signal, must be taken into account to compensate for magnetization transfer effects inherent in arterial spin tagging approaches that use a single radio-frequency coil. Two approaches that either correct for, or circumvent, the apparent upfield shift of the magnetization transfer spectrum are presented, and a perfusion image of the cat brain, using flow-induced adiabatic inversion of arterial water protons, is presented. Other problems in obtaining quantitative cerebral blood flow values using the arterial spin tagging approach are discussed.

Pre- and post-operative cerebral blood flow changes in subarachnoid haemorrhage

Assessment of cerebral perfusion on patients with subarachnoid haemorrhage (SAH) in the Neurologic Intensive Care Unit is difficult since nuclear medicine imaging modalities capable of measuring cerebral blood flow (CBF) are not generally available. We performed 101 quantitative (ml 100g-min) bedside CBF measurements on 40 individual patients to correlate SAH grade with CBF and to assess the effect of surgical intervention on CBF. Global CBF (G-CBF) and bihemispheric CBF (B-CBF) asymmetry were correlated with the grade of SAH pre- and post-operatively. Data analysis showed that pre-operative patients with low grade SAH (Hunt and Hess grades 0 to 2) had higher mean G-CBF values [44.2 +/- 71] than those with high grade SAH (Hunt and Hess grades 3 to 4): [mean G-CBF = 34.1 +/- 1.7]. Post-surgery there was a significant improvement in G-CBF; CBF increased [5.3 +/- 1.07] in the group of patients with low grade SAH. Patients with high grade SAH showed no significant improvement in their G-CBF during the first week post-operatively compared to pre-operative values. We conclude that portable units capable of measuring bedside CBF values are useful in monitoring CBF changes in patients with SAH. Patients with low grade SAH have G-CBF within normal limits both pre-operatively and post-operatively, with a statistically significant increase in CBF during two weeks post-operatively. Patients with high grade SAH show no significant increase in CBF one week post-operatively compared to their pre-operative measures.

The effect of vascular reconstructive surgery on the quantitative EEG and regional cerebral blood flow

The effect of vascular reconstructive surgery on the quantitative EEG and regional cerebral blood flow

Quantitative activation patterns of cerebral blood flow during mental stimulation after intravenous injection of 195mAu.

A previously reported theory for quantitative cerebral blood flow measurement for nondiffusible radiotracers has been applied to patients after stroke and to volunteers undergoing a mental stimulation exercise. Quantitative measurements of cerebral blood flow pattern in p-a and lateral projections of the brain are obtained using the short lived (30s) isotope 195mAu from the recently developed generator. The energy spectrum of the eluate from the generator shows two strong photon peaks, one at an energy level of 68 KeV and a second at 262 KeV. The low-energy peak is suitable for perfusion studies of the cerebral hemispheres in lateral projection, being without "look through" effect. The high-energy level is good for studies in the p-a-projection. Studies last less than 1 min and can be repeated after 3 min. Parametric images for quantitative regional cerebral blood flow can be generated, in which the avascular region following stroke can be detected. Quantitative activation patterns of cerebral blood flow during mental stimulation can be generated. The results show that it is possible to measure cerebral blood-flow patterns not only with freely diffusible indicators like Xenon but also with nondiffusible indicators.

Multichannel Miniature Semiconductor Detector System with On-Line Computer Analysis for Measurement of Miniregional Cerebral Blood Flow

This paper outlines our experience over the past decade, with a multichannel miniature semiconductor detector system for measurement of miniregional cerebral blood flow. 8 channels of a lithium drifted silicon detector system with on-line computer analysis are satisfactorily operating in monitoring quantitative regional cerebral blood flow on multisites of the brain in vivo in humans as well as animals. More recently, our experience with a highly gamma sensitive Cadmium Telluride detector (CdTe) was disappointing. For 133Xe clearance studies, the CdTe detector gave a 5 times higher counting efficiency than the Si(Li) detector. However, blood flow values obtained by Stochastic analysis from the CdTe detector are 25 to 40% less than the values obtained from the Si(Li) detector. This problem appears to be mainly due to a trapping phenomenon occurring in the CdTe detector which gives a non-linear response between radioactivity and count rate, and over exceeds random fluctuation of count rate. These genetic and temperamental features of the CdTe detector make it unsuitable for use in measurement of cerebral blood flow at the present time. Our clinical and laboratory experience with miniature semiconductor systems will be reviewed.