Use of [18F]fluorodeoxyglucose positron emission tomography in patients with primary malignant brain tumors

In patients with malignant gliomas, [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) may discriminate tumor progression from radionecrosis. We evaluated data from 50 patients undergoing FDG-PET for suspicion of tumor progression. Forty-nine were treated with surgery, 48 with radiotherapy, and 37 with chemotherapy. Twenty-one had intensive radiotherapy with either three daily treatments in two 5-day periods and intravenous carboplatin (17) or interstitial brachytherapy or stereotactic radiotherapy. Twenty underwent surgery after magnetic resonance imaging/FDG-PET; 9 demonstrated increased uptake of FDG and evidence of tumor, whereas 6 had decreased uptake and no evidence of tumor. In 5 patients, there was no correlation (all had intensive radiotherapy). In 17 patients who received bromodeoxyuridine intravenously just before surgery, the bromodeoxyuridine labeling index corresponded to the histological appearance in all but 2 patients (both had received intensive radiotherapy). In 30 patients without surgery, decreased uptake of FDG suggested prolonged survival; increased uptake of FDG did not predict survival. Eight of 10 with intensive radiotherapy had decreased label uptake. We conclude FDG-PET for evaluation of patients with possible recurrent tumors requires more study. In patients with intensive radiotherapy, FDG-PET results cannot be correlated accurately with tumor progression.     

Dynamic [18F]fluorodeoxyglucose positron emission tomography and hypometabolic zones in seizures: Reduced capillary influx

We performed dynamic [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomographic (PET) analyses in 8 patients. Rate constants of influx (K₁^*), efflux (k₂^*), phosphorylation (k₃^*), and dephosphorylation (k₄^*) were derived for the regions of interest (ROIs), which included (1) the hypometabolic epilptogenic regions and (2) the homologous regions in the contralateral hemispheres. In addition, the four constants were determined from at least one clearly defined (control) ROI from the same plane and its homologous contralateral ROI. (K₁^*) in the eplieptogenic region was reduced in comparison with the contralateral ROI. Reductions in influx (K₁^*), which averaged 18 ± 13% (mean ± SD), [¹⁸F]FDG phosphorylation (k₃^*) (25 ± 20%), and brain glucose utization rates (26 ± 10%) were observed in the epileptogenic region. Reductions in efflux were not statistically significant (k₂^* = 13 ± 28%) but were comparable in magnitude to the average reduction in K₁^*. No ipsilateral versus contralateral differnces were seen for any rate constants measured outside the epileptogenic region. Influx correlated highly with phosphorylation in the epileptogenic region. Our data suggest that the hypometabolic epileptogenic focus seen in [¹⁸F]FDG-PET studies is also a region of reduced blood-brain barrier glucose transporter activity and that reductions in phosphorylation are proportional to reductions in [¹⁸]FDG influx.     

The metabolic anatomy of Parkinson's disease: complementary [18F]fluorodeoxyglucose and [18F]fluorodopa positron emission tomographic studies

We studied the metabolic anatomy of typical Parkinson's disease (PD) using [18F]fluorodeoxyglucose (FDG) and [18F]fluorodopa (FDOPA) and positron emission tomography (PET). Fourteen PD patients (mean age 49 years) had FDG/PET scans, of which 11 were scanned with both FDOPA and FDG. After the injection of FDOPA, brain uptake and arterial plasma radioactivity were monitored for 2 h. Striatal FDOPA uptake was analyzed with regard to a two-compartment model, and target-to-background ratios (TBRs) and TBR-versus-time slopes were also calculated. Regional patterns of metabolic covariation were extracted from FDG/PET data using the Scaled Subprofile Model (SSM). SSM pattern weights, FDOPA uptake constants (Ki), TBRs, and TBR slopes were correlated with clinical measures for bradykinesia, rigidity, tremor, gait disturbance, left-right asymmetry, dementia, and overall disease severity. In PD patients, rate constants for FDOPA uptake correlated with individual measures of bradykinesia (p = 0.001) and gait disability (p less than 0.05). SSM analysis revealed a distinct pattern of regional metabolic asymmetries, which correlated with motor asymmetries (p less than 0.001) and left-right differences in Ki (p less than 0.01). Our data suggest that in PD patients, FDG/PET and FDOPA/PET may provide unique and complementary information about underlying disease processes.     

Neuropathological investigation of the hypometabolic regions on positron emission tomography with [18F] fluorodeoxyglucose in patients with dementia with Lewy bodies

We performed a quantitative neuropathological examination of the hypometabolic regions on FDG PET in dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and control cases. When the DLB cases were divided into two groups according to concomitant AD pathology (ADP), neuronal loss in the temporo-parietal association area was milder in the DLB groups than in the AD group, although there were no differences between the two DLB groups. Tau and Aβ immunoreactivities were observed in the AD group and the DLB group with ADP, but were rare in the DLB group without ADP. Tau and Aβ immunoreactivities as well as numbers of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) were more common in the AD group than in the DLB group with ADP. There was no difference in neuronal loss in the occipital area among the three groups. α-Synuclein immunoreactivity was observed in the DLB groups but not in the AD group. There were no differences in α-synuclein immunoreactivity and number of Lewy bodies (LBs) between the two DLB groups. These findings indicate that the neuropathological bases of the hypometabolic regions in the temporo-parietal association and occipital area in DLB may be AD pathology and Lewy pathology, respectively.     

Identification of early recurrence of primary central nervous system tumors by [18F]fluorodeoxyglucose positron emission tomography

As aggressive neurosurgery and adjuvant therapy have become standard care for most patients with primary central nervous system (CNS) tumors, limitations of posttreatment neuroimaging techniques have become more apparent. Interpretation of computed cranial tomography (CT) and magnetic resonance imaging (MRI) in patients with brain tumors is complicated by changes related to surgery, corticosteroids, radiation, and chemotherapy. We investigated the role of 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (FDG-PET) in these difficult diagnostic situations by obtaining FDG-PET scans in 5 patients following temporal lobectomy for epilepsy, in 5 patients with recurrent anaplastic gliomas before and after corticosteroid therapy, and in 5 patients after the development of histologically confirmed radionecrosis. We also obtained postoperative FDG-PET scans in 32 consecutive patients undergoing initial resection of a primary brain tumor. Our results indicate that glucose uptake as detected by FDG-PET scanning with [18F]fluorodeoxyglucose is not increased in the postoperative period; is not affected by steroid therapy; and accurately predicts early recurrence of tumor, supplementing other predictors of tumor behavior, including extent of resection, histological diagnosis, and postoperative CT. Thus PET using [18F]fluorodeoxyglucose can contribute to the optimum management of patients with primary brain tumors.     

Dopa-responsive dystonia: [18F]dopa positron emission tomography.

The syndrome of dopa-responsive dystonia comprises a minority of patients with dystonia, yet it is of considerable diagnostic importance because patients respond dramatically to L-dopa therapy. Benefits from this treatment are lasting, and the problems associated with long-term L-dopa therapy in patients with Parkinson's disease are generally absent. It has been suggested that this condition is due to a defect in the dopamine synthetic pathway, which is bypassed when patients are treated with L-dopa. We have studied [18F]dopa uptake in 6 patients with classic dopa-responsive dystonia (5 familial patients and 1 sporadic patient), aged 18 to 66 years. Data have been analyzed according to a graphic approach, calculating an influx constant for each region studied. We have also studied a seventh, clinically atypical, patient with juvenile dystonia-parkinsonism. Similar data have been calculated for a group of 10 healthy control subjects and 10 patients with Parkinson's disease. The 6 patients with typical dopa-responsive dystonia had a modest but significant reduction in the uptake of tracer into both caudate and putamen, which indicates a defect in the decarboxylation, vesicular uptake, and storage of [18F]dopa. This argues against the proposition that dopa-responsive dystonia is due to an inherited defect of tyrosine hydroxylase alone. In the atypical patient, however, we found a greater reduction of [18F]dopa uptake into both caudate and putamen, comparable with that in patients with Parkinson's disease.     

Differentiation of Alzheimer's disease from dementia with Lewy bodies utilizing positron emission tomography with [18F]fluorodeoxyglucose and neuropsychological testing

We compared the relative utility of neuropsychological testing and positron emission tomography (PET) with [18F]fluorodeoxyglucose ([18F]FDG) in differentiating Alzheimer's disease (AD) from dementia with Lewy bodies (DLB). We studied 25 patients with AD, 20 with DLB, and 19 normal elderly controls. There was no difference between patient groups for MMSE, confrontational naming, or verbal learning. The DLB group was significantly more impaired than the AD group for verbal fluency, and the AD group was significantly more impaired than the DLB group for verbal delayed recall. The DLB group had greater difficulty than the AD group on a visual discrimination task that does not require motor functioning, but the difference did not reach significance. Family ratings of motor functioning suggested significantly greater impairment in DLB patients than in AD patients. PET studies revealed significantly lower local cerebral metabolic rates for glucose (lCMRglc) for visual cortex (Brodmann areas 17, 18, and 19) in the DLB than the AD group, but no differences for other regions commonly affected in AD, including posterior cingulate, superior parietal lobe, lateral temporal lobe, and the prefrontal region. Motor ratings were significantly correlated with lCMRglc in all areas of cerebral cortex, including Brodmann areas 17, 18, and 19. The results demonstrate a similar profile of cerebral hypometabolism in the two patient groups except in the visual cortex, where the DLB group shows markedly lower lCMRglc than the AD group. Neuropsychological testing also differentiates the groups, and family ratings of motor functioning are as robust as PET in these later stages of the disorders.     

{18F}fluorodeoxyglucose positron emission tomography in refractory complex partial seizures

Positron emission tomography with simultaneous electroencephalographic monitoring was performed with {¹⁸F}fluorodeoxyglucose in 20 patients with complex partial seizures who had normal computed tomographic scans. Seven patients had only unilateral epileptiform discharges on the electroencephalogram, 3 had predominantly unilateral discharges, and 10 had nonlocalized epileptiform abnormalities. Positron emission tomography showed a hypometabolic lesion in 16 of the 20 patients. Pathological changes in the hypometabolic region were found in postoperative specimens in 4 of 5 patients studied. Positron emission tomography was unaffected by the seizure frequency, state of alertness, or number of spike discharges during the scan. There was a tendency for patients to have higher overall metabolic rates when taking less medication. Seizures occurring during {¹⁸F}fluorodeoxyglucose uptake in 3 patients produced a hypermetabolic area at the interictal hypometabolic focus. Positron emission tomography sometimes showed more widespread hypometabolism than suspected on the basis of the scalp-recorded electroencephalogram. The frontal lobe showed a greater degree of hypometabolism than the temporal lobe in 3 patients. Focal lesions may be identified by positron emission tomography even if the electroencephalographic abnormality is not well localized.     

Computed tomography,magnetic resonance imaging and positron emission tomography with [18F] fluorodeoxyglucose in multiple system atrophy and pure autonomic failure

We studied 45 patients who had autonomic failure with computed tomography, magnetic resonance imaging and positron emission tomography with [¹⁸F]fluorodeoxyglucose to characterize the neuroimaging features of multiple system atrophy and pure autonomic failure and determine the utility of these techniques in distinguishing multiple system atrophy from pure autonomic failure. There were 30 patients with multiple system atrophy and 15 with pure autonomic failure. In the multiple system atrophy group, eight patients had mainly cerebellar signs, seven extrapyramidal and 15 had combinations of cerebellar and extrapyramidal signs. Cerebellar atrophy on computerized tomography and magnetic resonance imaging, signal hypointensity in the posterolateral putamen on magnetic resonance imaging and a generalized reduction in glucose utilization rate with positron emission tomography with [¹⁸F]fluorodeoxyglucose, were the main findings and were seen only in the patients with multiple system atrophy. Decreased glucose utilization (hypometabolism) was most prominent in the cerebellum, brainstem, striatum and frontal and motor cortices. These results indicate clear differences, using neuroimaging studies, between multiple system atrophy and pure autonomic failure.     

Morphine-induced metabolic changes in human brain. Studies with positron emission tomography and [fluorine 18]fluorodeoxyglucose

Morphine sulfate effects (30 mg, intramuscularly) on cerebral glucose utilization and subjective self-reports were examined in 12 polydrug abusers by positron emission tomography and [fluorine 18]fluorodeoxyglucose in a double-blind placebo-controlled crossover study. During testing, subjects sat with eyes covered, listening to white noise and "beep" prompts. Morphine significantly reduced glucose utilization by 10% in whole brain and by about 5% to 15% in telencephalic areas and the cerebellar cortex, assuming no contribution of hypercapnia. When the contribution of PaCO2 (45 minutes after morphine was administered) was partialled out, significant morphine-induced reductions persisted in whole brain and six cortical areas. Irrespective of morphine, left-greater-than-right asymmetry occurred in the temporal cortex, and an interaction between hemisphere and drug was noted in the postcentral gyrus. In most cases, effects on glucose utilization were not significantly related to measures of euphoria.     

Mapping metabolic brain activation during human volitional swallowing: a positron emission tomography study using [18F]fluorodeoxyglucose.

We have previously shown that labelled water positron emission tomography (H2(15)O PET) can be used to identify regional cerebral blood flow (rCBF) changes in the human brain during volitional swallowing. (18F) fluorodeoxyglucose (FDG PET), by comparison, uses a glucose analogue to quantitatively measure regional cerebral glucose metabolism (rCMRglc) rather than rCBF. The main advantage of FDG PET is improved spatial resolution, and because of its pharmacodynamic properties, activation can be performed external to the scanner, allowing subjects to assume more physiologic positions. We therefore conducted a study of the brain's metabolic response while swallowing in the erect seated position, using FDG PET. Eight healthy male volunteers were studied with a randomised 2 scan paradigm of rest or water swallowing at 20-second intervals for 30 minutes. Data were analysed with SPM99 using multisubject conditions and covariates design. During swallowing, analysis identified increased rCMRglc (P<0.01) in the following areas: left sensorimotor cortex, cerebellum, thalamus, precuneus, anterior insula, left and right lateral postcentral gyrus, and left and right occipital cortex. Decreased rCMRglc were also seen in the right premotor cortex, right and left sensory and motor association cortices, left posterior insula and left cerebellum. Thus, FDG PET can be applied to measure the brain metabolic activity associated with volitional swallowing and has the advantage of normal task engagement. This has implications for future activation studies in patients, especially those suffering swallowing problems after brain injury.     

18F]fluorodeoxyglucose positron emission tomography in the diagnosis of cancer in patients with paraneoplastic neurological syndrome and anti-Hu antibodies

The diagnosis of cancer is often difficult in patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Fluorodeoxyglucose 18 positron emission tomography scanning is a highly sensitive and specific method to detect lung tumors. We investigated 15 patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Radiological methods led to the diagnosis of cancer in 12 patients, and test results were negative in 3. Whole-body [18F]fluorodeoxyglucose positron emission tomography showed abnormal uptake in the mediastinum in these 3 patients in accordance with the expected location of the malignancy.     

Effects of percent thresholding on the extraction of [18F]fluorodeoxyglucose positron emission tomographic region-of-interest data

Although we and others have employed a thresholding strategy to extract "peak" values from positron emission tomographic (PET) regions of interest (ROIs), the effects of peak picking on fitted fluorodeoxyglucose rate constants, regional metabolic rate for glucose (rCMRglc) profiles, patterns of regional metabolic covariation, and PET-neurobehavioral correlations have not been systematically investigated. Our results suggest that under some commonly encountered imaging conditions percent thresholding may increase sensitivity to regional activation; however, the effect of thresholding is determined by a number of factors, including the relative magnitude of regional activation, ROI size, and the specific threshold selected. The difference-annulus concept is proposed as a means to study the effects of different region drawing and thresholding strategies, and to determine if a given ROI contains one and only one source of covarying metabolic activity.     

Parametric mapping of [18F]fluoromisonidazole positron emission tomography using basis functions

In this study, we show a basis function method (BAFPIC) for voxelwise calculation of kinetic parameters (K₁, k₂, k₃, K_i) and blood volume using an irreversible two-tissue compartment model. BAFPIC was applied to rat ischaemic stroke micro-positron emission tomography data acquired with the hypoxia tracer [¹⁸F]fluoromisonidazole because irreversible two-tissue compartmental modelling provided good fits to data from both hypoxic and normoxic tissues. Simulated data show that BAFPIC produces kinetic parameters with significantly lower variability and bias than nonlinear least squares (NLLS) modelling in hypoxic tissue. The advantage of BAFPIC over NLLS is less pronounced in normoxic tissue. K_i determined from BAFPIC has lower variability than that from the Patlak–Gjedde graphical analysis (PGA) by up to 40% and lower bias, except for normoxic tissue at mid-high noise levels. Consistent with the simulation results, BAFPIC parametric maps of real data suffer less noise-induced variability than do NLLS and PGA. Delineation of hypoxia on BAFPIC k₃ maps is aided by low variability in normoxic tissue, which matches that in K_i maps. BAFPIC produces K_i values that correlate well with those from PGA (r²=0.93 to 0.97; slope 0.99 to 1.05, absolute intercept <0.00002 mL/g per min). BAFPIC is a computationally efficient method of determining parametric maps with low bias and variance.     

Positron emission tomography with [18F]fluorodeoxyglucose differentiates normal pressure hydrocephalus from Alzheimer-type dementia.

Because diagnostic criteria for normal pressure hydrocephalus have not been clearly determined, it is often difficult to differentiate patients with this potentially treatable condition from those with Alzheimer-type dementia. We have studied three patients with normal pressure hydrocephalus, 17 patients with Alzheimer-type dementia, and seven healthy elderly controls using positron emission tomography and [18F]Fluorodeoxyglucose (FDG). Both Alzheimer-type dementia and normal pressure hydrocephalus groups showed lower cortical rates of FDG utilisation than controls. However, the patterns of metabolic abnormality were distinctly different in the two dementia groups, with Alzheimer-type dementia subjects demonstrating bilateral temporoparietal hypometabolism while normal pressure hydrocephalus subjects showed globally diminished glucose use.     

EEG, transmission computed tomography, and positron emission tomography with fluorodeoxyglucose 18F. Their use in adults with gliomas

We evaluated the relationship between findings from EEG, transmission computed tomography (CT), and positron emission tomography in 23 adults with gliomas. The cortical metabolic rate was suppressed in patients with and without focal slowing. Focal delta activity was not related to involvement of gray or white matter. Rhythmic delta activity and focal attenuation of background amplitude on EEG, however, were correlated with involvement of the thalamus.     

Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F 18

Cerebral metabolic rates for glucose were examined in patients with unipolar depression (N = 11), bipolar depression (N = 5), mania (N = 5), bipolar mixed states (N = 3), and in normal controls (N = 9) using positron emission tomography and fluorodeoxyglucose F 18. All subjects were studied supine under ambient room conditions with eyes open. Bipolar depressed and mixed patients had supratentorial whole brain glucose metabolic rates that were significantly lower than those of the other comparison groups. The whole brain metabolic rates for patients with bipolar depression increased going from depression or a mixed state to a euthymic or manic state. Patients with unipolar depression showed a significantly lower ratio of the metabolic rate of the caudate nucleus, divided by that of the hemisphere as a whole, when compared with normal controls and patients with bipolar depression.