Evaluation of delayed appearance of acetazolamide effect in patients with chronic cerebrovascular ischemic disease: feasibility and usefulness of SPECT method using triple injection of ECD.

The purpose of this study was to verify the feasibility and usefulness of a new SPECT method, called triple injection of (99m)Tc-ethylcysteinate dimer (TIE), in evaluation of the delayed or poor appearance of acetazolamide (ACZ) effects in patients with chronic cerebral ischemic disease. METHODS: Three equal-volume splits of (99m)Tc-ethylcysteinate dimer were intravenously administered, and 1,000 mg ACZ were used as a vasodilator. A middle cerebral artery territory in the lateral ventricle was used as a region of interest. The data at rest and at 7.5 and 20 min after ACZ challenge (ACZ 7.5 and ACZ 20, respectively) were obtained by dynamic SPECT, and a time response curve to ACZ was obtained through the relative ratio of regional counts to the data at rest, not through regional cerebral blood flow. Nine cases of complete occlusion of the internal carotid artery (IC) and 6 cases of severe IC stenosis were analyzed. RESULTS: In 12 healthy volunteers (24 cerebral hemispheres) using a placebo (negative control), the values at rest and at rest 7.5 and rest 20 (corresponding to ACZ 7.5 and ACZ 20, respectively) were 100%, 100.4% +/- 2.8%, and 99.6% +/- 3.6%, respectively, indicating the accuracy of the TIE method. In a positive control using 24 normal cerebral hemispheres, prompt maximal vasoreactivity at ACZ 7.5 (124.5% +/- 8.0%) was confirmed, as was continuous vasoreactivity until ACZ 20 (130.1% +/- 12.8%). The values between ACZ 7.5 and ACZ 20 were not statistically different. Patients with complete IC occlusion exhibited a poor response at ACZ 7.5 despite a normal response at ACZ 20 (delayed response). Furthermore, in patients with severe IC stenosis, restoration of cerebrovascular reactivity after carotid endarterectomy was confirmed not only at ACZ 20 but also at ACZ 7.5. CONCLUSION: The TIE method using SPECT may be a potentially useful and sensitive strategy in clinical evaluation of the delayed or poor appearance of ACZ effects in patients with chronic cerebrovascular ischemic disease.     

Perfusion MRI before and after acetazolamide administration for assessment of cerebrovascular reserve capacity in patients with symptomatic internal carotid artery (ICA) occlusion: comparison with <Superscript>99m</Superscript>Tc-ECD SPECT

Introduction Impaired cerebral vascular reserve (CVR) in patients with symptomatic internal carotid artery (ICA) occlusion is regarded as a possible indication for performing extra-/intracranial (EC/IC) bypass surgery. As perfusion MR imaging (MRI) can demonstrate cerebral haemodynamics at capillary level, our hypothesis was that perfusion MRI could be used in these patients for the evaluation of CVR following acetazolamide challenge in a similar way to single photon emission CT (SPECT) and might provide additional information. Methods Enrolled in the study were 12 patients (mean age 61.3 years; 11 male, 1 female) with symptomatic unilateral ICA occlusion proven by angiography. Both perfusion MRI and 99m-technetium-ethyl-cysteinate dimer (^99mTc-ECD) SPECT were performed before and after injection of acetazolamide (Diamox ,1000 mg i.v.). CVR parameters including regional cerebral blood flow (rCBF) and volume (rCBV), and mean transit times (MTT) were measured by perfusion MRI. Results The patients with impaired CVR proven by SPECT (n = 9) had a negative mean rCBF increment (−46.52%), negative rCBV increment (−13.5%) and delayed MTT (mean +2.98 s), respectively, on the occluded side (Student’s t-test all P < 0.05). The patients with sufficient CVR (n = 3) had a mean rCBF increment of 1.2%, a decrement of rCBV of 10.46%, and a mean MTT shortening of 0.27 s following the acetazolamide injection. Conclusions Perfusion MRI before and after acetazolamide administration compares favourably with ^99mTc-ECD SPECT for the detection of impaired CVR. The impact that perfusion MRI studies (before and after acetazolamide administration) might have on the treatment decision in patients with ICA occlusion has yet to be determined by a prospective study. The first and second author contributed equally to this study.     

Evaluation of time dependency of the acetazolamide effect on cerebral hemodynamics as measured by 99mTc-ECD single-photon emission computed tomography

PURPOSE: Kuwabara et al. have examined the cerebral artery dilation with acetazolamide (ACZ) challenge test using PET. And, they reported that ACZ reaction came out time dependently. We have developed a unique SPECT's method using Technetium-99m ethyl cysteinate dimer (99mTc-ECD) to verify the results obtained by Kuwabara et al. METHOD: 1000 MBq of 99mTc-ECD was exactly divided into three syringes. Each of which was intravenous infused (i.v.) at rest, 7.5, and 20 minutes after ACZ administration. Data collection was started using dynamic SPECT immediately after 99mTc-ECD i.v. at rest. Using necessary data only, SPECT images representing each of the three 99mTc-ECD i.v. was reconstructed. SPECT counts were obtained by the ROI method from each images to calculate relative CBF from rest to 7.5 and 20 minutes after ACZ administration. RESULT: The 18 hemispheres of nine patients in the negative control group in whom ACZ was not loaded. CBF was stable during the three evaluation. The measurement error our method was estimated as small. The 18 hemispheres of nine patients in the positive control group who has normal vasodilatory reserve, CBF was increased by 26.2 +/- 8.1% at 7.5 minutes and 29.3 +/- 13.1% at 20 minutes after ACZ administration. Seven patients with and chronic stage unilateral internal carotid artery severe stenosis and/or occlusion were evaluated as the test group. Case of unaffected side, CBF was increased by 17.6 +/- 6.9% at 7.5 minutes and 24.8 +/- 11.3% 20 minutes after ACZ administration. And, increase rate of CBF in the affected side was 2.8 +/- 1.6% at 7.5 minutes and 17.3 +/- 5.0% at 20 minutes after ACZ administration. In the affected side, timing of the maximum CBF increase caused by ACZ was remarkably delayed. CONCLUSION: Our method based on 99mTc-ECD SPECT also revealed delayed cerebral artery dilation in the affected side. It was suggested that ACZ reaction came out time dependently, as reported by Kuwabara et al.     

Susceptibility-weighted MR for evaluation of vasodilatory capacity with acetazolamide challenge.

PURPOSETo investigate cerebral vasodilatory capacity by acetazolamide challenge in healthy subjects and in patients with chronic occlusive cerebrovascular disease by using susceptibility-weighted gradient-echo MR imaging.METHODSEight patients with chronic occlusive cerebrovascular disease and four healthy volunteers were studied with susceptibility-weighted MR imaging before and after intravenous administration of 1000 mg of acetazolamide. Signal intensities were measured as a function of time in several regions of interest defined on anatomic images. In all patients with chronic occlusive cerebrovascular disease, acetazolamide challenge and resting regional cerebral blood flow were also evaluated with single-photon emission CT (SPECT).RESULTSIn healthy volunteers, signal intensities began to increase 3 to 4 minutes after acetazolamide administration, with a continuous increase during the subsequent 10 minutes. The effect lasted for approximately 45 minutes after administration. In patients with chronic occlusive cerebrovascular disease, signal changes on susceptibility-weighted MR images of occluded areas with normal vasodilatory capacity on SPECT images did not differ from signal changes of nonocclusive areas. In those patients with changes that reflected diminished vasodilatory capacity, the MR images showed a lower percentage of signal changes after acetazolamide administration than those in normally perfused areas.CONCLUSIONSusceptibility-weighted MR imaging offers an alternative method for estimating vasodilatory capacity.     

Reduced perfusion reserve in Leukoaraiosis demonstrated using acetazolamide challenge 123I-IMP SPECT

OBJECTIVE: We examined the relationship between the perfusion reserve as measured by acetazolamide (ACZ)-challenge N-isopropyl-I-123-p-iodoamphetamine (IMP)-single-photon emission computed tomography (SPECT) and the degree of leukoaraiosis (LA) as estimated using magnetic resonance imaging. METHODS: In 51 patients receiving IMP-SPECT with the resting state and ACZ challenge, the unaffected cerebral hemispheres were included in the present study. Mean cerebral blood flow (CBF) in the resting state and ACZ reactivity were acquired. Absolute CBF value and ACZ reactivity were compared among patients with LA grades 0, 1, and 2. The relationship between mean age and LA grade was also assessed. RESULTS: No significant difference in the absolute CBF value in the resting state was observed among the 3 LA groups. Although vasoreactivity in LA grade 0 did not differ from that in grade 1, vasoreactivity in LA grade 2 was significantly lower (P < 0.05) than that in grades 0 or 1. CONCLUSIONS: The perfusion reserve is impaired in advanced LA.     

Clinical significance of cerebrovascular reserve in acetazolamide challenge —comparison with acetazolamide challenge H2O-PET and Gas-PET—

OBJECTIVE: The response of cerebral blood flow (CBF) to acetazolamide (ACZ) challenge is frequently determined in clinical settings to evaluate cerebrovascular reserve (CVR). A reduced CVR can indicate patients with occlusive cerebrovascular disease and compromised hemodynamics who may be at increased risk of cerebral ischemia. However, how precisely ACZ reflects cerebral hemodynamic impairment remains obscure. The present study aims to clarify the pathological significance of CVR in patients with occluded carotid arteries. METHODS: We recruited seventeen patients with occlusive lesions in the internal carotid artery (ICA) or middle cerebral artery (MCA). We assessed these patients in terms of resting cerebral blood flow (CBF) and the CVR response to ACZ challenge using H20 positron emission tomography (PET). In addition, we evaluated hemodynamic parameters including oxygen extraction fraction (OEF) using Gas-PET. RESULTS: We identified a significant negative correlation between the CVR and OEF or the cerebral blood volume (CBV)/CBF ratio, as a potential index of cerebral perfusion pressure. Although the CVR values were reduced in all regions with elevated OEF (Stage II), these values were highly variable regardless of the CBV/CBF ratios. The cut-off value of CVR alone could not detect Stage II, but when combined with resting CBF, misery perfusion accompanied by increased OEF was detected with high sensitivity (6/7) and specificity (61/62). CONCLUSION: CVR could be applied as an index reflecting both autoregulatory capacity and OEF. The present study also supported the notion that SPECT with ACZ challenge can be clinically applied to detect misery perfusion.     

Sequential change of hemodynamic reserve in patients with major cerebral artery occlusion or severe stenosis

Summary To identify regional vasodilatory capacity and its sequential change, we evaluated prospectively a total of 78 acetazolamide tests in 51 patients with occlusion or greater than 75% stenosis of the carotid or middle cerebral arteries. The relative distribution of cerebral blood flow was determined by single photon emission computed tomography usingN-isopropyl-p-[¹²³I]-iodoamphetamine before and after intravenous injection of acetazolamide. Reduced vasodilatory capacity was demonstrated in 20 patients (38%), including 5 patients with hemodynamic transient ischemic attacks or infarction. Follow-up acetazolamide tests revealed asymptomatic progression of the arterial lesion (from stenosis to occlusion) in 1 patient and almost complete improvement of vasodilatory capacity in 5 patients, including 3 without surgical intervention. During an average follow-up period of 18.5 months, 4 patients died from cardiac causes or neoplasm; no neurovascular events occurred. Much larger numbers of patients with longer observation periods will be necessary to clarify the contribution of chronic hemodynamic failure to subsequent stroke. However, the present data indicate that the acetazolamide test is useful for assesssing the course of high grade stenosis or occlusion of major cerebral arteries.     

Can the detection of misery perfusion in chronic cerebrovascular disease be based on reductions in baseline CBF and vasoreactivity?

Purpose: The aim of this study was to clarify whether decreases in baseline regional cerebral blood flow (rCBF) and in residual cerebral vasoreactivity (CVR), assessed by the acetazolamide (ACZ) challenge, can detect misery perfusion in patients with chronic cerebrovascular disease (CVD). Methods: Oxygen extraction fraction (OEF) and other haemodynamic parameters were measured in 115 patients (64±9 years old) with unilateral cerebrovascular steno-occlusive disease (>70% stenosis) using ¹⁵O-gas and water PET. A significant elevation of OEF, by greater than the mean+2SD compared with healthy controls, was defined as misery perfusion. CBF, CVR determined by percent change in CBF after ACZ administration, OEF and other haemodynamic parameters in the territories of the bilateral middle cerebral arteries were analysed. Diagnostic accuracy for the detection of misery perfusion using the criteria determined by baseline CBF and CVR was evaluated in all patients and in only those patients with occlusive lesions. Results: Ten of 24 patients with misery perfusion showed a significant reduction in CVR. Using criteria determined by significant decreases in CVR and baseline CBF, misery perfusion was detected with a sensitivity of 42% and a specificity of 95% in all patients. In patients with occlusive lesions (n=50), sensitivity was higher but specificity was slightly lower. The diagnostic accuracy of the threshold determined by baseline CBF alone was similar in all patients and in only those patients with occlusive lesions, and was higher than that achieved using the asymmetry index of OEF. Conclusion: Reductions in CVR and baseline CBF in the ACZ challenge for CVD would detect misery perfusion with high specificity. Reduction in baseline rCBF is more accurate than reduction in CVR alone for the detection of misery perfusion.     

Differences in vasodilatory capacity and changes in cerebral blood flow induced by acetazolamide in patients with cerebrovascular disease.

To investigate changes in cerebral blood flow (CBF) and blood volume induced by acetazolamide (ACZ) in patients with a variable autoregulatory status responding to reduced perfusion pressure, PET measurements of hemodynamic parameters were performed on patients with cerebrovascular disease, and the relationships between the parameters were evaluated. METHODS: Sixteen patients with unilateral major cerebral arterial occlusive disease underwent PET studies with (15)O-gas and the steady-state method to obtain hemodynamic parameters in the brain. All patients and 8 healthy volunteers underwent H(2)(15)O PET at baseline and 10 min after ACZ injection to calculate the CBF and arterial-to-capillary blood volume (V(0)) based on a 2-compartment model. RESULTS: The regional CBF (rCBF) and V(0) increased significantly after ACZ administration in volunteers and in the hemisphere contralateral to the ischemic side in patients. However, in a subgroup of patients with disease who showed a significant reduction in the rCBF increase in the ipsilateral hemisphere, the ACZ challenge caused a decrease in the rCBF even though the V(0) showed a significant increase. The reduction in the rCBF increase was associated with an asymmetric increase in oxygen extraction fraction (OEF) but not with an absolute OEF increase. CONCLUSION: The increases in rCBF and V(0) induced by ACZ administration, as well as absolute OEF value in the baseline condition, did not necessarily parallel each other in the ipsilateral hemispheres of patients. Thus, the increase in rCBF after ACZ challenge may not represent vasodilatory capacity in patients with cerebrovascular disease, especially in the regions with a reduced rCBF response.     

Assessment of cerebral hemodynamics before and after revascularization in patients with occlusive cerebrovascular disease by means of quantitative IMP-SPECT with double-injection protocol

The purpose of this study was to validate a double-injection (DI) method with N-isopropyl-[123I]p-iodoamphetamine (IMP) to measure regional cerebral blood flow (rCBF) twice in a single session of dynamic SPECT and to elucidate a possible role of this method to identify patients with occlusive disease of major cerebral arteries, who might benefit from cerebral revascularization procedures (CR). MATERIALS AND METHODS: Fourteen patients with occlusion or severe stenosis of the internal carotid or middle cerebral artery were studied before and after CR to assess hemodynamic changes after revascularization treatment. We quantitatively measured rCBF before and after acetazolamide (ACZ) challenge along with cerebrovascular reserve capacity (CVR) with two injections of IMP in a single session of dynamic SPECT scans (DI method). The reliability and reproducibility of the DI method were validated by means of a simulation study and in eight patients who were examined without ACZ challenge to measure baseline rCBF twice. RESULTS: The analysis of simulated noisy data with realistic noise levels showed that the errors of the estimates for the first and the second rCBF and for the increase in rCBF were 2.6%, 8.1% and 10.4%, respectively. In the 8 patients examined by the DI method to measure baseline rCBF twice, the mean and the SD of percentage differences between the two consecutive measurements in rCBF were -1.3% and 5.5%, respectively. Eight out of 14 patients with occlusive disease had at least one region with a CVR less than 10%. They showed a significant increase in resting rCBF after CR, not only in the ipsilateral hemisphere (from 26.1 +/- 6.4 to 33.4 +/- 4.7) but also in the contralateral one (from 28.3 +/- 7.0 to 34.7 +/- 4.7) with a recovery of the ipsilateral CVR from 9.3 +/- 17.2 to 41.2 +/- 20.1%. The remaining six patients with good-moderate CVR did not show an increase in rCBF after CR (from 28.0 +/- 2.7 to 28.3 +/- 3.4). The three of them with a moderate CVR (10-25%) before CR showed normalization of CVR after CR. CONCLUSION: Patients with decreased rCBF and reduced CVR benefited from CR in terms of an increase in rCBF and recovery of CVR. The quantitative double-injection IMP-SPECT has the ability to identify those patients who may benefit from CR.     

Acetazolamide-challenged perfusion magnetic resonance imaging for assessment of cerebrovascular reserve capacity in patients with symptomatic middle cerebral artery stenosis: comparison with technetium-99m-hexamethylpropyleneamine oxime single-photon emission computed tomography

Objectives

Acetazolamide-challenged perfusion magnetic resonance imaging (MRI) has been shown as a method for assessment of cerebrovascular reserve (CVR) capacity in patients with atherosclerotic steno-occlusive disease of internal carotid artery. We have assessed the feasibility of the acetazolamide-challenged perfusion MRI for evaluating CVR in symptomatic patients with severe middle cerebral artery (MCA) stenosis (≥70%) by comparison with the acetazolamide-challenged technetium-99m-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT).

Methods

Seventeen prospectively enrolled patients with symptomatic unilateral MCA stenosis underwent technetium-99m-hexamethylpropyleneamine oxime SPECT and perfusion MRI without and with acetazolamide challenge, respectively. Acetazolamide-challenged SPECT and perfusion MRI were compared quantitatively by Region of interest (ROI) analysis.

Results

At all ROIs, there were no significant differences in percent change between SPECT and perfusion MRI. Patients with impaired CVR showed significant decreases in the percent changes of respective cerebral blood flow (P=.016) and respective cerebral blood volume (P=.029).

Conclusion

Acetazolamide-challenged perfusion MRI is feasible for evaluating CVR in symptomatic patients with severe MCA stenosis quantitatively.     

Relationship between vasodilatation and cerebral blood flow increase in impaired hemodynamics: a PET study with the acetazolamide test in cerebrovascular disease.

The changes in cerebral blood flow (CBF) and arterial-to-capillary blood volume (V(0)) induced by acetazolamide (ACZ) are expected to be parallel each other in the normal circulation; however, it has not been proven that the same changes in those parameters are observed in patients with cerebrovascular disease. To investigate the relationship between changes in CBF, vasodilatory capacity, and other hemodynamic parameters, the ACZ test was performed after an (15)O-gas PET study. METHODS: Twenty-two patients with unilateral major cerebral arterial occlusive disease underwent PET scans using the H(2)(15)O bolus method with the ACZ test after the (15)O-gas steady-state method. CBF and V(0) for each subject were calculated using the 3-weighted integral method as well as the nonlinear least-squares fitting method. After evaluation of accuracy in V(0) values, a new parameter, the CBF/V(0) ratio, which is expected to disclose arterial perfusion pressure, was also compared between the conditions. RESULTS: The regional CBF (rCBF) and V(0) increased significantly after ACZ administration in the hemisphere contralateral to the ischemic side. However, in a subgroup of patients who showed a significant reduction in the rCBF increase in the ipsilateral hemisphere (group A), the ACZ injection caused no change or a slight decrease in rCBF even though the V(0) showed a significant increase. Thus, the increases in rCBF and V(0) did not necessarily parallel each other in the ipsilateral hemispheres of patients who have impaired cerebral circulation. A parameter defined by the rCBF/V(0) ratio decreased significantly in the ipsilateral hemisphere of group A after ACZ administration, although the ratio showed no change in the contralateral hemisphere or in the other subgroup (group B). CONCLUSION: The change in the rCBF/V(0) ratio after ACZ challenge may represent an alteration in arterial perfusion pressure that is expected to indicate a critical hemodynamic status in patients with cerebrovascular disease, especially in patients who have a reduced rCBF response.     

Acetazolamide induced myocardial ischemia in patients with severe coronary artery disease

Acetazolamide (ACZ)-augmented brain SPECT is commonly used for evaluating cerebral vascular reserve in patients with cerebrovascular disease. ACZ may cause myocardial ischemia in patients with coronary artery disease. To evaluate the risk of induction of myocardial ischemia with ACZ-augmented myocardial SPECT, we performed combined ACZ-augmented Tl-201 myocardial SPECT (ACZ-myo SPECT) with Tc-99m HMPAO brain SPECT in patients with severe coronary artery disease.Methods: Nine patients underwent combined ACZ-myo SPECT with Tc-99m HMPAO brain SPECT. (1) For qualitative analysis, SPECT images were divided into 13 segments to calculate the total defect scores. (2) Six ROIs were placed on the slices in the myocardial SPECT short-axis images and the regional uptake ratio was obtained as the ratio of the mean counts in the myocardium to the maximal count in the slice. The total defect score and regional uptake ratio of ACZ-myo SPECT were compared with those of early and delayed dipyridamole T1-201 myocardial SPECT (DP-T1 SPECT) images.Results: (1) In the 21 coronary artery territories with coronary stenosis ≧ 75%, the total defect score in ACZ-myo SPECT, early and delayed DP-T1 SPECT images were 3.52 ± 4.14*, 4.19 ± 4.65* and 2.25 ± 3.34, respectively (*: p < 0.05 vs. delayed DP-Tl SPECT images). (2) In 44 of 54 ROIs with coronary stenosis ≧75%, the regional uptake ratio of ACZ-myo SPECT, early and delayed DP-Tl SPECT images were 0.670 ± 0.166**, 0.677 ± 0.194**, 0.721 ± 0.178, respectively (**: p < 0.01 vs. delayed DP-Tl SPECT images). Systolic blood pressure fell at 11 min after ACZ infusion without electrocardiographic ST-T changes or chest pain.Conclusion: As ACZ has the potential to cause myocardial ischemia, ACZ-augmented brain SPECT should be performed with caution in patients with severe coronary artery disease associated with cerebrovascular disease.     

Directional atherectomy in iliac stent failure: Clinical technique and histopathologic correlation

Purpose: To assess the feasibility and efficacy of directional atherectomy in the treatment of iliac stent stenosis or occlusion and to evaluate the histologic composition of excised atherectomy specimens. Methods: Directional atherectomy of six occluded and 10 severely stenosed iliac stents was undertaken in 12 patients at a mean interval of 28 months (range 3–69 months) after stent insertion for occlusive aortoiliac disease. In cases of stent occlusion, atherectomy was preceded by low-dose thrombolysis. In all patients stent clearance with return of femoral pulses was achieved within 24 hr and there were no significant complications. All excised specimens were sent for histologic examination. Results: Eleven patients (92%) remain symptom free with unlimited walking distance at a mean follow-up interval of 11.5 months (range 3–31 months) after treatment. Histologic examination revealed typical myointimal hyperplasia at three excision sites, intimal fibrosis at three sites, atheroma at four sites and organized thrombus at six sites. Conclusion: Atherectomy offers an effective treatment in iliac stent occlusion and restenosis with no significant adverse effects. Debulking of these lesions seems to offer a more logical approach than simple balloon angioplasty. Clinical and duplex follow-up confirms satisfactory outcome within the first year but longer-term results are not yet known. The histologic data obtained demonstrate that stent restenosis and occlusion are likely to be multifactorial, and challenge the assumption that myointimal hyperplasia is the sole cause of iliac stent occlusion.     

Carotid artery disease: evaluation with acetazolamide-enhanced Tc-99m HMPAO SPECT.

Sixty patients were studied for carotid artery disease and were further evaluated with hexamethyl-propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) both at baseline (with the patient resting) and after administration of acetazolamide (ACZ). Of these 60 patients, 58 (97%) had symptoms and 49 (82%) had stenoses greater than 70% in at least one internal carotid vessel. Nine patients (15%) had symmetric findings on baseline examinations and at SPECT with ACZ. Thirty-two patients (53%) had asymmetric findings on baseline, but in 24 of these patients (75%) additional lesions were observed after ACZ administration. Nineteen patients (32%) had asymmetric findings only after ACZ was administered. HMPAO SPECT with ACZ allows detection of diminished cerebral perfusion reserve that is not found when HMPAO SPECT is performed with the patient at rest. This procedure helps provide an objective evaluation of the hemodynamic effects of carotid stenosis.     

Correlative assessment of hemodynamic parameters obtained with T2*-weighted perfusion MR imaging and SPECT in symptomatic carotid artery occlusion

BACKGROUND AND PURPOSE: Perfusion MR imaging and single-photon emission CT (SPECT) are commonly used to evaluate hemodynamic status in patients with symptomatic occlusive cerebrovascular disease. These techniques rely on different underlying physiological mechanisms, and the data may not correspond. We studied the relationship between hemodynamic parameters obtained with these two methods. METHODS: We performed perfusion MR imaging and SPECT in 10 patients with symptomatic unilateral internal carotid artery occlusion. Relative cerebral blood volume (rCBV) and uncorrected mean transit time (uMTT) were obtained with dynamic contrast-enhanced T2*-weighted MR imaging. Relative cerebral blood flow (rCBF) and vascular reserve capacity were measured with 99mTc-HMPAO SPECT; vascular reserve capacity was calculated by the difference in CBF before and after acetazolamide challenge. Ratios of these hemodynamic parameters between the affected and contralateral vascular territories were calculated and compared. RESULTS: Normal-to-increased CBV, prolonged uMTT, decreased CBF, and normal-to-diminished vascular reserve capacity were observed in the affected vascular territories. Reduction of vascular reserve capacity corresponded well with uMTT but not with CBF and CBV. CBF, CBV, and uMTT did not correspond to one another. CONCLUSION: uMTT is more sensitive than the other parameters in estimating vascular reserve capacity. The relationship between parameters obtained with perfusion MR imaging and SPECT should be considered in assessing the hemodynamic status of patients with symptomatic occlusive cerebrovascular disease.     

SPECT evaluation of cerebral blood flow during arm exercise in patients with subclavian steal

Objectives To explore the cerebral hemodynamics in subclavian steal syndrome, we examined the cerebral perfusion of seven patients with subclavian steal (one symptomatic and six asymptomatic) using single-photon emission computed tomography (SPECT) during resting, arm exercise, and acetazolamide-activated conditions. Methods The regional CBF (rCBF) was measured with SPECT under all conditions, and region of interest (ROI) analysis was performed using a three-dimensional stereotaxic ROI template (3DSRT). We evaluated the relationship between arm exercise-induced rCBF change and (1) presence of subclavian artery stenosis, (2) vertebral reverse flow severity, (3) presence of vertebro-basilar insufficiency (VBI) symptoms, and (4) cerebrovascular reactivity (CVR) to acetazolamide. Results Overall, no arm exercise-induced rCBF reduction was observed on either the affected or the unaffected side, even in patients with severe vertebral reverse flow. One patient with VBI symptoms showed an arm exercise-induced global rCBF reduction in the cerebrum and cerebellum, whereas the other asymptomatic patients did not. The %rCBF changes in segments with severely impaired CVR (−8.6%± 10.7%, mean ± SD) were significantly lower than those in other segments with less impaired CVR (P < 0.01). Conclusions Our results suggest that subclavian steal is a benign condition in asymptomatic patients. On the other hand, arm exercise-induced rCBF reduction can occur in the cerebrum and cerebellum in patients with VBI symptoms possibly related to low CVR.     

Cerebellar vasoreactivity in stroke patients with crossed cerebellar diaschisis assessed by acetazolamide and 99mTc-HMPAO SPECT.

Crossed cerebellar diaschisis (CCD) tends to persist or even worsen after supratentorial infarction. Several studies have shown impairment of cerebral vasomotor responsiveness in the hemispheric area of diaschisis in patients with hemispheric infarction. This finding has led to the concern that the lack of CCD reversibility might be associated with chronic circulatory abnormalities. We therefore assessed the vasoreactivity in the cerebellar hemisphere in which diaschisis is manifested using acetazolamide (ACZ) and SPECT. METHODS: Eight stroke patients with CCD (5 with unilateral hemispheric infarcts and 3 with unilateral intracerebral hemorrhage) had 99mTc-HMPAO SPECT scanning at rest and 20 min after intravenous injection of 1.0 g ACZ. The time interval after stroke ranged from 25 to 904 d. From the total counts obtained from each cerebellar hemisphere, the asymmetry index (AI) was calculated as (unaffected - affected cerebellar hemisphere)/unaffected cerebellar hemisphere x100. RESULTS: After ACZ, the mean AI (8.7+/-6.6) was significantly decreased (P<0.05) compared with that at rest (17.7+/-5.8). Seven of the 8 patients showed decrease in the AI after ACZ. In 1 patient, the direction of the asymmetry was reversed after ACZ so that the AI was negative. The ACZ-induced change in the AI did not show a significant correlation with the time interval after stroke, whether calculated in absolute terms or as a percentage change. CONCLUSION: This study shows that normal vascular supply is maintained in the CCD-affected cerebellar hemisphere over long periods of time after a stroke. Thus, the lack of CCD reversibility may not be attributed to a chronic circulatory insufficiency. The results lend support to the concept of functional deactivation and subsequent transneuronal degeneration as a likely explanation for CCD. It is unclear whether decreased AI after ACZ indicates a higher vascular response of the affected cerebellar hemisphere than that of the normal side.     

Which CT Perfusion Parameter Best Reflects Cerebrovascular Reserve?: Correlation of Acetazolamide-Challenged CT Perfusion with Single-Photon Emission CT in Moyamoya Patients

BACKGROUND AND PURPOSE: CT perfusion (CTP) is a more readily accessible method for evaluation of cerebral perfusion than single-photon emission CT (SPECT). We assessed whether there is any resting or drug-challenged CTP parameter correlating with cerebrovascular reserve (CVR) obtained by SPECT in Moyamoya patients.MATERIALS AND METHODS: Normalized baseline CTP parameters and their percentage changes were calculated in 152 regions of interest (ROIs). On qualitative SPECT analysis, each ROI was classified in either the “impaired CVR” or “normal CVR” group. Quantitative CVR was calculated by using normalized SPECT values before and after acetazolamide administration. Baseline CTP parameters and their percentage changes were compared with qualitative and quantitative CVRs. Receiver operating characteristic (ROC) curve analysis defined the threshold values of CTP parameters that best predict impaired qualitative CVR.RESULTS: The mean values of CTP parameters were significantly different between normal and impaired CVR groups. The percentage change of cerebral blood flow (pcCBF) was correlated most significantly with quantitative CVR (r = 0.89; P < .05). The correlation coefficients between the baseline CTP parameters and quantitative CVR were poor or not significant. The ROC-derived threshold values of pcCBF and mean transit time determined impaired CVR with a sensitivity of 94.4 and 85.2; specificity of 93.2 and 65.9; positive predictive value of 97.1 and 86.0; and negative predictive value of 87.2 and 64.4, respectively.CONCLUSION: Baseline CTP parameters are not reliable for predicting impaired CVR. However, pcCBF correlated strongly with quantitative CVR; therefore, CTP evaluation for CVR in Moyamoya patients requires normalization and acetazolamide challenge.

Quantitative assessment of cerebrovascular reserve (CVR) to acetazolamide (ACZ) can determine the severity of hemodynamic impairment in patients with major cerebral artery occlusive disease.¹ The risk of developing an ischemic event is known to be higher in patients with reduced CVR than in those with preserved CVR.^2,3 Under physiologic conditions, ACZ increases cerebral blood flow (CBF); however, the degree of cerebral vessel dilation is lower in areas of reduced cerebral perfusion pressure, because the cerebral vessels are already dilated.⁴ As a result, ACZ-challenged single-photon emission CT (SPECT) increases the contrast in radioactivity levels between regions of adequate vascular reserve and those of inadequate reserve, and CVR obtained by using SPECT provides important information for hemodynamic status in patients with chronic cerebrovascular occlusive diseases.⁵ However, SPECT has to be performed usually in a 2-day setting due to tracer kinetics. Moreover, it provides less morphologic information than CT or MR imaging. On the other hand, CT perfusion (CTP) is a much more readily accessible imaging method for assessing the hemodynamic status in patients with cerebral steno-occlusive arterial disease and can provide both morphologic and hemodynamic information in a single investigation. Feasibility of CTP in the evaluation of patients with chronic cerebral ischemia has been attempted in several studies.^6,7Several hemodynamic parameters, such as cerebral blood volume (CBV), mean transit time (MTT), and CBF, can be acquired by CTP. Dilation of precapillary resistance vessels increases CBV; therefore, increase of CBV may be an initial indicator of a fall in cerebral perfusion pressure and reduction of CVR.³ In some studies, CBV or MTT has been measured to detect the presence of autoregulatory vasodilation, and MTT has been suggested to be more sensitive than CBV.^6,8 Kaneko et al⁸ and Lythgoe et al⁹ showed that quantitative measurement of MTT by using a deconvolution algorithm can be a sensitive and reliable indicator of the cerebral perfusion reserve capacity, and it provides important information for the management of patients with occlusive cerebrovascular diseases.In the present study, we compared the baseline and drug-challenged parameters obtained by ACZ-CTP with CVR obtained by SPECT to determine which CTP parameter best reflected CVR.     

Usefulness of brain SPECT to evaluate brain tolerance and hemodynamic changes during temporary balloon occlusion test and after permanent carotid occlusion.

The purpose of this study was to evaluate the usefulness of SPECT during temporary carotid balloon occlusion testing and to evaluate the changes in regional cerebral blood flow (CBF) and regional cerebral perfusion reserve (CPR) after permanent carotid occlusion. METHODS: Temporary balloon occlusion testing was performed on 40 patients (24 head and neck tumors, 16 aneurysms). During the balloon occlusion (total time, 30 min), (99m)Tc-ethylcysteinate dimer (ECD) was injected intravenously about 5 min before balloon deflation, followed by SPECT data acquisition. SPECT images were visually evaluated, and the severity of hypoperfusion on the occluded side was classified using 4 grades (normal, mild, moderate, and severe). The count ratio of the occluded side to the contralateral side (L/N ratio) was also analyzed. In 7 patients who subsequently underwent permanent carotid occlusion, CBF and CPR were quantitatively assessed using (133)Xe inhalation dynamic SPECT at rest and after acetazolamide (ACZ) enhancement (CPR was defined as the percentage increase in CBF after ACZ), and the patients were followed up periodically. RESULTS: SPECT after temporary occlusion showed moderate or severe hypoperfusion in 12 patients, whereas neurologic deterioration was observed in only 4 patients. The L/N ratios were 0.96 +/- 0.03 in normal perfusion (13 patients), 0.93 +/- 0.03 in mild hypoperfusion (15 patients), 0.83 +/- 0.03 in moderate hypoperfusion (10 patients) and 0.66 +/- 0.09 in severe hypoperfusion (2 patients) (P < 0.0001). In the 7 patients who underwent permanent carotid occlusion, CPR decreased after surgery (35% +/- 7% vs. 7% +/- 14%, P < 0.05), even though the resting CBF did not change (54 +/- 8 mL/100 g/min vs. 52 +/- 6 mL/100 g/min, not statistically significant). The steal phenomenon (rCPR < 0%) was observed in 3 patients, 1 of whom experienced transient hemiparesis when blood pressure dropped soon after surgery. On follow-up, the decreased CPR gradually improved and no infarction developed. CONCLUSION: SPECT is useful to detect cerebral hypoperfusion during carotid occlusion. Assessment of CPR is recommended to predict the potential risk of postsurgical complications and to follow up patients after permanent carotid occlusion.