High reproducibility of regional abnormalities on interictal123I-IMP SPECT brain scans in adults with partial epilepsy

Summary The reproducibility of twoN-isopropyl-(iodine 123)p-iodoamphetamine (¹²³I-IMP single photon emission computed tomography (SPECT) scans both taken during interictal periods was studied in 13 adult patients with partial epilepsy who had normal CT scans. The frequency of the seizures and the nature of the ictal symptoms were virtually unchanged during the interval between the two SPECT scans performed in each case. In 8 (72.7%) of 11 patients who had abnormal images consisting of focal hypofixation images of¹²³I-IMP, i.e. zones of decreased regional cerebral blood flow on the first scans, complete or partial regional reproduction of the SPECT abnormalities was observed. This high reproducbility supports the usefulness of SPECT scans in the regional diagnosis of epileptic foci.     

Reproducibility of cerebral blood flow assessment using a quantitative SPECT reconstruction program and split-dose (123)I-iodoamphetamine in institutions with different γ-cameras and collimators

Single photon emission computed tomography (SPECT) is used widely in clinical studies. However, the technique requires image reconstruction and the methods for correcting scattered radiation and absorption are not standardized among SPECT procedures. Therefore, quantitation of cerebral blood flow (CBF) may not be constant across SPECT models. The quantitative SPECT (QSPECT) software package has been developed for standardization of CBF. Using the QSPECT/dual-table autoradiographic (DTARG) method, CBF and cerebral vascular reactivity (CVR) at rest and after acetazolamide challenge can be evaluated using (123)I-iodoamphetamine in a single SPECT session. In this study, we examined the reproducibility of quantitative regional CBF and CVR in QSPECT/DTARG using different SPECT models at two facilities. The subjects were nine patients with chronic cerebral ischemic disease who underwent QSPECT/DTARG at both facilities with use of different γ-cameras and collimators. There were significant correlations for CBF at rest and after acetazolamide challenge measured at the two facilities. The consistency of the CBFs of the patients measured at the two facilities were good in all cases. Our results show that CBF measured by QSPECT/DTARG in the same patients is reproducible in different SPECT models. This indicates that standardized evaluation of CBF can be performed in large multicenter studies.     

Possible impact of dopamine SPECT on decision-making for drug treatment in Parkinsonian syndrome

Summary. Single-photon emission computed tomography (SPECT) markers allow measuring the integrity of the brain dopaminergic system in vivo. We used dopamine transporter (DAT) SPECT with [¹²³I]FP-CIT and dopamine D₂/D₃ receptor SPECT with [¹²³I]IBZM to evaluate whether there is a reduction of DAT and/or D₂/D₃ receptor SPECT in treated and untreated patients with Parkinsonian syndrome (PS). We found that almost a quarter of our patients treated with anti-Parkinsonian medication prior to SPECT imaging did not show evidence of a presynaptic dopaminergic deficit while 37% of untreated patients were diagnosed as having Parkinson’s disease. 17% of treated patients had additional loss of D₂/D₃ receptor binding capacity in concordance with the clinical follow-up diagnoses of multiple system atrophy, progressive nuclear palsy, and vascular Parkinsonism. Apart from 38% clinically uncertain cases, SPECT was in concordance with 75% of initial clinical diagnoses. 25% were reclassified as indicated by SPECT findings and confirmed by a 1.5-year clinical follow-up. We conclude that dopamine SPECT may support establishing or refuting the clinical diagnosis and, therefore, help to make the decision for or against dopaminomimetic treatment in cases with PS.     

Evaluation of the GABAergic nervous system in autistic brain: (123)I-iomazenil SPECT study

Purpose

To evaluate the GABA_A receptor in the autistic brain, we performed ¹²³I-IMZ SPECT in patients with ASD. We compared ¹²³I-IMZ SPECT abnormalities in patients who showed intellectual disturbance or focal epileptic discharge on EEG to those in patients without such findings.

Subjects and methods

The subjects consisted of 24 patients with ASD (mean age, 7.3 ± 3.5 years), including 9 with autistic disorder (mean age, 7.0 ± 3.7 years) and 15 with Asperger’s disorder (mean age, 7.5 ± 3.2 years). We used 10 non-symptomatic partial epilepsy patients (mean age, 7.8 ± 3.6 years) without intellectual delay as a control group.For an objective evaluation of the ¹²³I-IMZ SPECT results, we performed an SEE (Stereotactic Extraction Estimation) analysis to describe the decrease in accumulation in each brain lobule numerically.

Results

In the comparison of the ASD group and the control group, there was a dramatic decrease in the accumulation of ¹²³I-IMZ in the superior and medial frontal cortex. In the group with intellectual impairment and focal epileptic discharge on EEG, the decrease in accumulation in the superior and medial frontal cortex was greater than that in the group without these findings.

Conclusion

The present results suggest that disturbance of the GABAergic nervous system may contribute to the pathophysiology and aggravation of ASD, since the accumulation of ¹²³I-IMZ was decreased in the superior and medial frontal cortex, which is considered to be associated with inference of the thoughts, feelings, and intentions of others (Theory of Mind).     

Preservation of autoregulatory cerebral vasodilator responses to hypotension after inhibition of nitric oxide synthesis

Effects of inhibition of nitric oxide (NO) synthesis on the cerebrovascular autoregulatory vasodilator response to hypotension were studied in conscious rats. Cerebral blood flow (CBF) was determined with [¹⁴C]iodoantipyrine in a saline-treated control group and in three groups following inhibition of NO synthase activity by twice daily intraperitoneal injections of 50 mg/kg ofN^G-nitro-l-arginine methyl ester (l-NAME) for four days. In the saline-control group (n = 8) and in thel-NAME-treated Group (a) (n = 8) CBF was determined while systemic mean arterial blood pressure (MABP) remained at its resting level (means ± S.D., 128±6 and 151±11 mmHg, respectively). In the other groups CBF was determined after MABP was reduced by blood withdrawal to 118±9 and 88±8 mmHg in Groups (b) (n = 8) and (c) (n = 8), respectively. Despite the elevated MABP, global CBF was significantly lower inl-NAME-treated Group (a) than in the saline-controls (P < 0.005), indicating cerebral vasoconstriction striction resulting from inhibition of NO synthesis. Global CBF was not significantly reduced further in the two groups with hypotension. Local CBF in the hypotensive rats showed no significant reductions below values inl-NAME-treated control rats (Group (a)) in 31 of 32 brain structures; the only exception was in the auditory cortex of the severely hypotensive rats (Group (c)). The autoregulatory mechanism for cerebral vasodilatation to compensate for reduced arterial blood pressure is maintained following inhibition of NO synthesis.     

Interindividual variations of cerebral blood flow, oxygen delivery, and metabolism in relation to hemoglobin concentration measured by positron emission tomography in humans

Regional cerebral blood flow (CBF) and oxygen metabolism can be measured by positron emission tomography (PET) with ¹⁵O-labeled compounds. Hemoglobin (Hb) concentration of blood, a primary determinant of arterial oxygen content (C_aO₂), influences cerebral circulation. We investigated interindividual variations of CBF, cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO₂) in relation to Hb concentration in healthy human volunteers (n=17) and in patients with unilateral steno-occlusive disease (n=44). For the patients, data obtained only from the contralateral hemisphere (normal side) were analyzed. The CBF and OEF were inversely correlated with Hb concentration, but CMRO₂ was independent of Hb concentration. Oxygen delivery defined as a product of C_aO₂ and CBF (C_aO₂ CBF) increased with a rise of Hb concentration. The analysis with a simple oxygen model showed that oxygen diffusion parameter (L) was constant over the range of Hb concentration, indicating that a homeostatic mechanism controlling CBF is necessary to maintain CMRO₂. The current findings provide important knowledge to understand the control mechanism of cerebral circulation and to interpret the ¹⁵O PET data in clinical practice.     

Left superior temporal blood flow increases in schizophrenic and schizophreniform patients with auditory hallucination: A longitudinal case study using123I-IMP SPECT

Summary Serial assessments of regional cerebral blood flow were performed using¹²³I-IMP SPECT in two schizophrenic and three schizophreniform patients with persistent auditory hallucination. The initial SPECT study in the period with prominent auditory hallucination revealed an increased accumulation of¹²³I-IMP in the left superior temporal area which corresponded to the auditory association cortex. In the follow-up SPECT study performed after clinical improvement, the distribution of¹²³I-IMP had normalized. One of the case with schizophrenia showed a similar increased uptake of¹²³I-IMP in the left superior temporal area in the third SPECT scan performed when a psychotic relapse with auditory hallucination occurred. MRI scans in two of the five patients demonstrated reduced volume of the temporal lobes. These findings suggest that the auditory hallucinations in schizophrenia may be involved in functional hyperactivity in the left superior temporal cortex which might be based partly on structural abnormalities in the temporal lobes.     

Positron emission tomography/magnetic resonance hybrid scanner imaging of cerebral blood flow using 15O-water positron emission tomography and arterial spin labeling magnetic resonance imaging in newborn piglets

Abnormality in cerebral blood flow (CBF) distribution can lead to hypoxic–ischemic cerebral damage in newborn infants. The aim of the study was to investigate minimally invasive approaches to measure CBF by comparing simultaneous ¹⁵O-water positron emission tomography (PET) and single TI pulsed arterial spin labeling (ASL) magnetic resonance imaging (MR) on a hybrid PET/MR in seven newborn piglets. Positron emission tomography was performed with IV injections of 20 MBq and 100 MBq ¹⁵O-water to confirm CBF reliability at low activity. Cerebral blood flow was quantified using a one-tissue-compartment-model using two input functions: an arterial input function (AIF) or an image-derived input function (IDIF). The mean global CBF (95% CI) PET-AIF, PET-IDIF, and ASL at baseline were 27 (23; 32), 34 (31; 37), and 27 (22; 32) mL/100 g per minute, respectively. At acetazolamide stimulus, PET-AIF, PET-IDIF, and ASL were 64 (55; 74), 76 (70; 83) and 79 (67; 92) mL/100 g per minute, respectively. At baseline, differences between PET-AIF, PET-IDIF, and ASL were 22% (P<0.0001) and −0.7% (P=0.9). At acetazolamide, differences between PET-AIF, PET-IDIF, and ASL were 19% (P=0.001) and 24% (P=0.0003). In conclusion, PET-IDIF overestimated CBF. Injected activity of 20 MBq ¹⁵O-water had acceptable concordance with 100 MBq, without compromising image quality. Single TI ASL was questionable for regional CBF measurements. Global ASL CBF and PET CBF were congruent during baseline but not during hyperperfusion.     

Brain blood flow during hypercapnia in fish: no role of nitric oxide

Very little is known about the regulation of cerebral blood flow (CBF) in lower vertebrates, especially fish. In mammals, hypercapnia causes cerebral vasodilation and increased CBF through mechanisms that involve the production of nitric oxide (NO). We have used epi-illumination microscopy in vivo to observe effects of hypercapnia on venular erythrocyte velocity, used as an index of CBF velocity, in rainbow trout (Oncorhynchus mykiss) and crucian carp (Carassius carassius). Rainbow trout exposed to a pCO₂ of 7.5 mmHg displayed a small increase of CBF velocity in two out of five fishes, while dorsal aortic blood pressure (P_DA) did not change. Exposing trout to a pCO₂ of 22.5 mmHg, resulted in an 80% increase in CBF velocity and a 21% increase in P_DA. Trout exposed to a pCO₂ of 75 mmHg showed an additional increase in blood pressure, while no further increase was seen in CBF velocity compared to a pCO₂ of 22.5 mmHg. By contrast, no change in CBF velocity was seen in crucian carp, even at a pCO₂ of 75 mmHg. None of the circulatory changes seen in the trout could be blocked by superfusing the brain surface with the NO synthase blocker N^G-nitro- -arginine. The results point at striking species differences in the responses of CBF and P_DA to hypercapnia in fish, and that the hypercapnia induced increase in CBF velocity seen in rainbow trout is independent of NO production.     

Early and delayed SPECT images of extracerebral fluid collection in infants using 123I-N-isopropyl-p-iodoamphetamine

Cerebral blood flow in seven infants with extracerebral fluid collections was investigated using single photon emission computed tomography (SPECT) with ¹²³I-N-isopropyl-p-iodoamphetamine. Early and delayed SPECT imaging was carried out. Areas of hypoperfusion were observed in five cases. The watershed zone of the major cerebral arteries or the territory of the anterior cerebral arteries were common areas of low perfusion. The hypoperfusion area was redistributed in two cases with intracranial hypertension. Subduroperitoneal shunts produced improvement of clinical symptoms in these cases. Hypoperfusion without redistribution was observed in three patients. In these areas, permanent tissue damage caused by a primary disease existed. Normal circulation patterns were observed in two patients. They showed normal development and follow-up CT revealed a decrease in the size of the extracerebral fluid collection. Measurement of regional cerebral blood flow may be helpful in considering surgical indications and in following up extracerebral fluid collection in infants.     

Role of nitric oxide in regulation of cerebral microvascular tone and autoregulation of cerebral blood flow in cats

The role of nitric oxide in the regulation of cerebrocortical microvascular tone and autoregulation of cerebral blood flow (CBF) was examined in 24 anesthetized cats. The local cerebral blood volume (CBV), mean transit time of blood (MTT), and CBF in the cortex were measured by our photoelectric method. CBV represents the cumulative dimensions of the cerebral microvessels. Intravenous injection of 0.35–0.7 mg/kg/minN^G-monomethyl-l-arginine (l-NMMA), an inhibitor of nitric oxide synthesis, significantly increased mean arterial blood pressure (MABP; 8.4–14.1%,P < 0.01), decreased CBV (15.2–28.7%,P < 0.01), and decreased CBF (20.0–29.8%,P < 0.01) in a dose-related manner. The changes in MABP, CBV, and CBF elicited byl-NMMA were inhibited (P < 0.05) by simultaneous infusion of 35 mg/kg/minl-arginine. Autoregulation of CBF was examined during controlled hypotension of −30 to −40 mmHg (artificial bleeding) and recovery of blood pressure (reinfusion of blood). Although CBF remained constant with blood pressure changes in the control state (ΔCBF/ΔMABP of 0.037±0.155 with hypotension), CBF became dependent on blood pressure changes (ΔCBF/ΔMABP of 0.478±0.135, P < 0.05) during infusion of 0.35 mg/kg/minl-NMMA. It is concluded that nitric oxide participates in both the regulation of basal tone of cerebral microvessels and the autoregulation of CBF.     

Quantitative evaluation of cerebral metabolites and cerebral blood flow in patients with carotid stenosis

Abstract

We examined the metabolic and hemodynamic status of patients with severe carotid stenosis and evaluated the effectiveness of carotid endarterectomy (CEA) by comparing pre- and post-operative results of quantitative proton magnetic resonance spectroscopy (¹H-MRS) and single-photon emission computed tomography (SPECT). Quantitative ¹H-MRS and SPECT were performed in 17 patients with severe carotid stenosis before CEA; in 10 patients the examinations were repeated after CEA. There was a significant correlation between the degree of internal carotid artery (ICA) stenosis and the N-acetyl-aspartate (NAA) concentration, and between CBF and NAA in the basal ganglia. In 10 of the 17 patients (58.8%) we noted a decrease of NAA on ¹H-MRS. After CEA in these patients, NAA was significantly increased, and in 7 of 8 patients whose pre-operative SPECT had indicated impairment of cerebral vasoreactivity, it was improved. Quantitative ¹H-MRS and CBF measurements can indicate the severity of metabolic and hemodynamic impairment in patients with severe carotid stenosis, and can help to assess the effectiveness of CEA. [Neurol Res 2001; 23: 573-580]     

Imaging of serotonin transporters and its blockade by citalopram in patients with major depression using a novel SPECT ligand [123I]-ADAM

Summary. We studied the midbrain SERT availability in patients with major depression and assessed the relation of SERT occupancy by citalopram to the treatment response. 21 non-medicated patients with major depression and 13 healthy controls were examined by [¹²³I]-ADAM SPECT. The midbrain SERT availability (SERT V₃″) was calculated using individual MRI scans. In 13/21 patients SPECT was repeated 7 days after oral medication with citalopram (10 mg/day). We found no significant difference in the mean midbrain SERT availability between the studied patients with major depression and healthy controls (0.86 ± 0.27 vs. 0.71 ± 0.44, p = 0.069). The mean SERT occupancy accounted to 61%. The degree of SERT blockade by citalopram did not correlate with the reduction in HAMD total score. Treatment with low-dosed citalopram caused individually variable occupancy of the midbrain-SERT and a rapid clinical improvement in 54% of the investigated patients.     

Neuropsychological tests and [99mTc]-HM PAO SPECT in the diagnosis of Alzheimer's dementia

Twenty-three patients with Alzheimer's dementia (AD) in relatively early stages and 40 patients with other cognitive disorders of vascular or degenerative aetiology underwent neuropsychological examination and [^99mTc]-HM PAO single photon emission computed tomography (SPECT). In contrast to the commonly accepted notion of a posterior temporoparietal reduction of tracer uptake as the typical SPECT pattern of AD, the most consistent feature found in the SPECT images of our AD patients was a hippocampal uptake deficit, associated with a variable degree of temporal, parietal and frontal deficit (extending from the posterior to the anterior regions), according to the severity of the disease. These results support the theory of AD as a hippocampal dementia, at least in the early stages. Neuropsychological tests were found to be somewhat more specific and more accurate than SPECT in distinguishing AD from non-AD cases.     

Use of a single [<Superscript>123</Superscript>I]-FP-CIT SPECT to predict the severity of clinical symptoms of Parkinson disease

The aim of this study was to assess the ability of a single SPECT performed in the early stage of Parkinson’s disease (PD) to predict disease severity in 19 patients with early PD. [¹²³I]-FP-CIT striatal uptake was expressed as a ratio of specific:nonspecific uptake for defined brain areas. Clinical severity was determined by the UPDRS at baseline and 12–15 months following the SPECT procedure. [¹²³I]-FP-CIT uptake in the contralateral putamen and striatum was correlated with UPDRS score at baseline, with a more significant correlation after 1-year interval. [¹²³I]-FP-CIT uptake in all areas was correlated with bradykinesia and rigidity subscores only at follow up visit. Significant correlations were found between [¹²³I]-FP-CIT uptake in the contralateral striatum, putamen and caudate and the difference between motor scores of 1-year interval (ΔUPDRS). These results suggest that disease severity might be anticipated by a single SPECT at an early stage of the disease.     

Measurement of myocardial accumulation of123I-metaiodobenzylguanidine for studying cardiac autonomic neuropathy in diabetes mellitus

The association of myocardial¹²³I-metaiodobenzylguanidine (MIBG) accumulation and autonomic neuropathy, as well as factors known to affect autonomic nervous function, were studied in a group of 12 diabetic patients representing different degrees of autonomic failure. The early myocardial uptake phase of¹²³I-MIBG was measured by calculating the peak net influx rate for the first 30 min after the¹²³I-MIBG injection and by single photon emission computed tomography (SPECT) imaging 1 h after the injection. The retainment of¹²³I-MIBG in the myocardium was measured using SPECT imaging 6 h after the injection, and myocardial uptake and the myocardium/liver uptake ratio were calculated. The 6-h myocardium/liver uptake ratio of¹²³I-MIBG was significantly (p<0.05) lower in the diabetic patients with clinically evident autonomic neuropathy compared with those without autonomic neuropathy. Geater body mass index was associated with lower peak net influx rate and 1-h myocardial uptake of¹²³I-MIBG, and greater diastolic blood pressure was associated with lower 1-h myocardial uptake of¹²³I-MIBG, whether or not the patients had diabetic autonomic neuropathy. In conclusion, reduction in the 6-h myocardium/liver uptake ratio of¹²³I-MIBG is related to diabetic autonomic neuropathy. Because the early¹²³I-MIBG accumulation in myocardium is reduced in diabetic patients with greater body mass index and diastolic blood pressure, irrespective of autonomic neuropathy, our results encourage the use of the late myocardial accumulation of¹²³I-MIBG for studying sympathetic neuropathy in the diabetic heart.     

Role of Peripheral Adenosine A1 Receptors in the Regulation of Sleep Apneas in Rats

The effects of administration of N⁶-p-sulfophenyladenosine (p-SPA), a peripheral adenosine A₁ receptor agonist, and 8-(p-sulfophenyl)theophylline (p-SPT), a peripheral adenosine A₁ receptor blocker, on spontaneous apneas were studied in 10 adult Sprague–Dawley rats by monitoring respiration, sleep, and blood pressure for 6 h. Intraperitoneal injection of p-SPA (1 mg/kg) to rats suppressed spontaneous central apneas during non-rapid eye movement sleep by 50% in comparison to control recordings (p = 0.03). This effect was blocked by pretreatment with an equimolar dose of p-SPT (0.67 mg/kg) indicating that p-SPA suppression of apneas was receptor mediated in the peripheral nervous system. Administration of p-SPA did not affect apnea expression in rapid eye movement sleep and had no effect on sleep or blood pressure at the dose tested. Administration of p-SPT (0.67, 6.7, and 30 mg/kg) to rats had no effect on apneas, sleep, or blood pressure. The lack of p-SPT effect on sleep apneas argues against a physiologic role for endogenous adenosine in the peripheral nervous system as a modulator of sleep apnea expression under baseline conditions.     

Usefulness of a blood flow analyzing program 3DSRT to detect occipital hypoperfusion in dementia with Lewy bodies

In the latest criteria for the clinical diagnosis of dementia with Lewy bodies (DLB), supportive features include generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity. In this study, we investigated the usefulness of a cerebral blood flow (CBF) quantification program '3DSRT' in detecting occipital hypoperfusion in DLB. Twenty two patients with probable DLB, 38 patients with probable Alzheimer's disease (AD) and 16 normal controls underwent brain perfusion SPECT. Compared with AD, DLB patients had a bilateral lower CBF in the posterior cerebral segments. The correlation of clinical symptoms and brain blood perfusion was examined by dividing the subjects into subgroups. DLB patients with Parkinsonism, when compared to non-Parkinsonism subgroup, had a lower CBF throughout the cerebrum with statistical significance in the posterior cerebral segments. The quantitative analysis of brain perfusion SPECT by 3DSRT could be a useful supportive measurement in the diagnosis of DLB.     

SPECT and epilepsy with continuous spike waves during slow-wave sleep

Ten cases of epilepsy with continuous spike waves in slow-wave sleep (CSWS) were evaluated using single photon emission computed tomography (SPECT); in eight patients the EEG paroxysmal abnormalities showed a predominant localization. SPECT carried out using^99mTc-HMPAO allows study of cerebral blood flow (CBF); the examination was performed during phases of drowsiness and the results compared to the EEG data. In four cases SPECT revealed areas of low CBF in sites corresponding to those of the prevalent EEG discharges; in two cases the areas of hypoperfusion did not correspond to those indicated by the EEG; lastly, in four cases SPECT results were negative. The areas of hypoperfusion were predominantly located in the frontal, temporal, and parietal regions. Furthermore, the percentage of positive SPECT results was significantly higher (five cases out of six) in the group in which the CSWS phase was prolonged for at least 1 year, compared to the group in which this phase lasted less than 1 year. Thus, in this type of epilepsy, SPECT reveals focal cortical areas of decreased CBF which correlated generally to the predominant sites of EEG abnormalities. A longer duration of the CSWS phase seems to be associated with a more significant cortical disorder, documented by the presence of areas of hypoperfusion.