Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer.

Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[(18)F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([(11)C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m(-2)·min(-1)) to 3-h saline infusion. Lean controls (n = 10) were compared with glycemically controlled volunteers with T2DM (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption (P = 0.04) and perfusion (P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids (P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions (P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups (P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM (P = 0.003). Myocardial work efficiency was lower in T2DM (P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM.

Melanoma patients evaluated by four different positron emission tomography reconstruction techniques.

One hundred and nineteen patients with malignant melanoma were studied using 2-[ F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET). The images were reconstructed using ordered subset expectation maximization with and without attenuation correction and filtered backprojection with and without attenuation correction. The most probable draining lymph node chains were surgically explored and the tumour volume was quantified at histology. The four different reconstructions of the PET images were retrospectively graded on a five-point scale by two blind readers and compared with the tumour volume. The readers agreed within +/-1 grade 93% (529/568) of the time. Comparing the areas under the receiver operating characteristic (ROC) curves gave 0.698, 0.668, 0.694 and 0.684 for the four reconstruction techniques. The lowest value comparing any pair of the four reconstruction techniques was P=0.371. Thus, none of the reconstruction techniques gave significantly better results than any of the others. The sensitivity of detection was 85% for tumour volumes of 113 m or more (about 6 mm in diameter), but only 4% for tumours less than this size. It can be concluded that the use of attenuation correction gives aesthetically more pleasing images, but the sensitivity and specificity are not significantly improved.

A study of persistent post-concussion symptoms in mild head trauma using positron emission tomography.

BACKGROUND: Complaints of persistent cognitive deficits following mild head trauma are often uncorroborated by structural brain imaging and neuropsychological examination. OBJECTIVE: To investigate, using positron emission tomography (PET), the in vivo changes in regional cerebral uptake of 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) and regional cerebral blood flow (rCBF) in patients with persistent symptoms following mild head trauma. METHODS: Five patients with mild head trauma and five age and education matched healthy controls were imaged using FDG-PET to measure differences in resting regional cerebral glucose metabolism. Oxygen-15 labelled water (H(2)(15)O)-PET was also used to measure group differences in rCBF changes during a spatial working memory task. In addition, neuropsychological testing and self report of dysexecutive function and post-concussion symptoms were acquired to characterise the sample. RESULTS: There was no difference between patients and controls in normalised regional cerebral FDG uptake in the resting state in frontal and temporal regions selected a priori. However, during the spatial working memory task, patients had a smaller increase in rCBF than controls in the right prefrontal cortex. CONCLUSIONS: Persistent post-concussive symptoms may not be associated with resting state hypometabolism. A cognitive challenge may be necessary to detect cerebral changes associated with mild head trauma.

Assessment of dietary therapies in a canine model of Batten disease.

The neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative diseases that occur in a number of animal species, including dogs. A study was conducted to determine whether the resupply of nutrients lost in NCL English Setter dogs would modify the course of the disease. Carnitine and polyunsaturated fatty acids have been reported to be reduced in NCL English Setters. Therefore, the normal laboratory diets of NCL dogs were supplemented with carnitine, fish oil and corn oil and the disease progression was compared with that of an untreated litter mate. The following specific prognostic indicators of NCL were monitored: cognitive function, brain atrophy, brain glucose metabolism and lifespan. Carnitine, with or without lipid supplements, dramatically delayed the progression of cognitive decline in NCL dogs. When fish oil and corn oil only were supplied, brain atrophy was reduced. A combination of all three supplements preserved cognitive function and increased lifespan by 10%. However, brain glucose hypometabolism and cerebral atrophy were not reduced. The results in this study indicated that the effectiveness of therapeutic interventions can be assessed by non-invasive methods at a relatively early stage of the disease process. Our study suggests that dietary supplementation with carnitine is a promising new approach for delaying or preventing the cognitive decline in dogs, and perhaps, with human NCL patients.

Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis.

UNLABELLED: Balloon catheters filled with liquid radioisotopes provide excellent dose homogeneity for intracoronary radiation therapy but are associated with risk for rupture or leakage. We hypothesized that the safety of liquid-filled balloons may be improved once positron emitters with half-lives below 2 h are used instead of the high-energy beta-emitters 166Ho, 186Re, or 188Re, all of which have a longer half-life of at least 17 h. METHODS: To support this concept, the suitability of 18F (half-life, 109.8 min), 68Ga (half-life, 67.6 min), 11C (half-life, 20.4 min), 13N (half-life, 9.97 min), and 15O (half-life, 2.04 min) for intracoronary radiation therapy was evaluated. Potential tissue penetration of positron radiation was assessed in a series of phantom experiments using Gafchromic film. Antiproliferative efficacy of positrons emitted by 68Ga was investigated in vitro using cultured bovine aortic smooth muscle cells (BASMCs), and was compared with gamma-radiation emitted by 137Cs. To characterize the remaining risk, we estimated radiotoxicity after accidental intravascular balloon rupture on the basis of tabulated isotope-specific doses (ICRP 53) and compared these values with 188Re. RESULTS: Half-dose depth of tissue penetration measured in phantom experiments was 0.29 mm for 18F, 0.42 mm for 11C, 0.54 mm for 13N, 0.79 mm for 15O, and 0.9 mm for 68Ga. Irradiation of cultured BASMCs with positron radiation (68Ga) induced dose-dependent inhibition of proliferation with complete proliferative arrest at doses exceeding 6 Gy. ED(50) and ED(80) were 2.5 +/- 0.4 Gy (mean +/- SD) and 4.4 +/- 0.8 Gy, respectively. Antiproliferative efficacy was equal to that of the 662-keV gamma-radiation emitted by 137Cs (ED(50), 3.8 +/- 0.2 Gy; ED(80), 8.0 +/- 0.3 Gy). Estimates made for patient whole-body and organ doses were generally below 50 mSv/1.85 GBq for all investigated positron emitters. The same dose estimates for 188Re were 6-20 fold higher. CONCLUSION: Among the studied radioisotopes, 68Ga is the most attractive source for liquid-filled balloons because of its convenient half-life, sufficient positron energy (2.92 MeV), documented antiproliferative efficacy, and uncomplicated availability from a radioisotope generator. The safety profile for 68Ga is significantly better than that of 188Re, which suggests this radioisotope should be evaluated further in preclinical studies.

Automated PET attenuation correction model for functional brain imaging.

UNLABELLED: The failure to compensate for subject motion between attenuation correction scans and emission scans precludes the optimization of functional brain imaging techniques. We have developed an automated method for attenuation correction that compensates for subject motion by deriving each set of correction factors from the corresponding emission study. METHODS: The technique consists of generation of an estimated skull image by filtered backprojection of the reciprocal of an emission sinogram; estimation of the thickness and radius of the skull on profiles extracted from the image; scaling the radius and thickness values to generate a model of the brain, skull, and scalp; and assignment of attenuation coefficients to the head model for generation of attenuation correction factors. Values for scale factors and tissue attenuation coefficients were determined empirically by fitting the emission-derived head model to measured transmission data in five subjects using nonlinear regression (group A). The average model parameters, across five datasets (group A), were then used to generate attenuation maps for five independent emission studies (group B). Mean-squared-error values were calculated between the measured transmission data and the two model groups. For comparison, mean squared error values were calculated between the measured transmission data and homogeneous ellipses that were manually fitted to emission images. RESULTS: The difference between the mean squared error for groups A and B was not significant (P>0.8), indicating that model parameters from a small group can be used for other subjects without further fitting. The mean squared error for the automated method was significantly lower than that of the ellipse method (P<0.001). The method reduced emission image variance, resulting in a higher peak Z value in activation images. The elimination of measured transmission scans resulted in a reduction in scan time ( approximately 15 min) and radiation exposure ( approximately 0.5-1.6 mrem). CONCLUSION: We have developed an automated attenuation correction method that compensates for subject motion between scans, accurately reproduces the characteristics of the head, and eliminates the use of measured transmission data to reduce scan duration, statistical noise propagation, and radiation dose.

Liquid-filled balloon brachytherapy using (68)Ga is effective and safe because of the short 68-minute half-life: results of a feasibility study in the porcine coronary overstretch model.

BACKGROUND: Liquid-filled balloons for coronary brachytherapy provide significant advantages over solid sources in dose homogeneity but carry the risk of life-threatening radiointoxication after balloon rupture and laboratory contamination in case of a spill. We hypothesized that the positron emitter (68)Ga, with a half-life of only 68 minutes, was well suited to overcome these safety obstacles while providing full therapeutic efficacy. METHODS AND RESULTS: The feasibility, efficacy, and safety of (68)Ga liquid-filled balloon brachytherapy were investigated in the porcine coronary overstretch model. Four groups of 5 balloon-induced coronary lesions were irradiated with 8, 12, 16, and 24 Gy targeted to the adventitia. Ten unirradiated lesions served as controls. Segments treated with 16 or 24 Gy exhibited marked suppression of neointimal proliferation at 28-day follow-up, with quantitative parameters of intraluminal proliferation reduced to <20%. This beneficial effect was not compromised by untoward edge effects. Uninjured but irradiated vessels did not show histological signs of radiation damage. The (68)Ga whole-body dose due to balloon rupture was estimated to be 5 rem/50 mCi treatment activity and compared favorably with that of (188)Re (78 rem/50 mCi). CONCLUSIONS: (68)Ga positron radiation suppresses neointimal proliferation at doses of 16 and 24 Gy. This biological efficacy, coupled with the attractive safety profile, suggests the selection of (68)Ga as an attractive isotope for liquid-filled balloon brachytherapy.

Functional heterogeneity of inferior frontal gyrus is shaped by linguistic experience.

A crosslinguistic, positron emission tomography (PET) study was conducted to determine the influence of linguistic experience on the perception of segmental (consonants and vowels) and suprasegmental (tones) information. Chinese and English subjects (10 per group) were presented binaurally with lists consisting of five Chinese monosyllabic morphemes (speech) or low-pass-filtered versions of the same stimuli (nonspeech). The first and last items were targeted for comparison; the time interval between target tones was filled with irrelevant distractor tones. A speeded-response, selective attention paradigm required subjects to make discrimination judgments of the target items while ignoring intervening distractor tones. PET scans were acquired for five tasks presented twice: one passive listening to pitch (nonspeech) and four active (speech = consonant, vowel, and tone; nonspeech = pitch). Significant regional changes in blood flow were identified from comparisons of group-averaged images of active tasks relative to passive listening. Chinese subjects show increased activity in left premotor cortex, pars opercularis, and pars triangularis across the four tasks. English subjects, on the other hand, show increased activity in left inferior frontal gyrus regions only in the vowel task and in right inferior frontal gyrus regions in the pitch task. Findings suggest that functional circuits engaged in speech perception depend on linguistic experience. All linguistic information signaled by prosodic cues engages left-hemisphere mechanisms. Storage and executive processes of working memory that are implicated in phonological processing are mediated in discrete regions of the left frontal lobe.

Olfactory-evoked regional cerebral blood flow in Alzheimer's disease.

Olfaction is impaired in Alzheimer's disease (AD). It was hypothesized that AD would reduce olfactory-evoked perfusion in mesial temporal olfactory (piriform) cortex, where neuropathology begins. Seven AD patients and 8 elderly controls (ECs) underwent olfactory threshold and identification tests and olfactory stimulation during positron emission tomography. Odor identification was impaired in AD, but threshold was not. Olfactory stimulation in ECs activated right and left piriform areas and right anterior ventral temporal cortex. AD patients had less activation in right piriform and anterior ventral temporal cortex but not in the left piriform area. Although orbital cortex did not activate in ECs, there was a significant between-groups difference in this area. Right piriform activation correlated with odor identification. Impaired odor identification likely reflects sensory cortex dysfunction rather than cognitive impairment. Given olfactory bulb projections to the mesial temporal lobe, olfactory stimulation during functional imaging might detect early dysfunction in this region.

Quantitative comparison of functional contrast from BOLD-weighted spin-echo and gradient-echo echoplanar imaging at 1.5 Tesla and H2 15O PET in the whole brain.

Spin-echo and gradient-echo echoplanar functional magnetic resonance imaging (fMRI) studies at 1.5 Tesla (T) were used to obtain blood oxygenation level-dependent (BOLD) contrast images of the whole brain in seven strongly right-handed women during execution of a complex motor task. Five subjects underwent subsequent H215O positron emission tomography (PET) studies while performing the same task. Group-averaged results for changes in the MRI relaxation rates R2* and R2 at 1.5T in response to neuronal activation in nine cortical, subcortical, and cerebellar motor regions are reported. Results for each method are grouped according to tissue type-cerebral cortex (precentral gyrus and supplementary motor area), subcortical regions (thalamus and putamen), and cerebellar cortex (superior lobule). The observed changes in R2* from activation-induced oxygenation changes were more variable across brain regions with different tissue characteristics than observed changes in R2. The ratio of deltaR2* to deltaR2 was 3.3 +/- 0.9 for cerebral cortex and 2.0 +/- 0.6 for subcortical tissue. deltaR2*, deltaR2, and relative blood flow changes were deltaR2* = -0.201 +/- 0.040 (s-1), deltaR2 = -0.064 +/- 0.011 s(-1), and deltaf/f = 16.7 +/- 0.8% in the cerebral cortex; deltaR2* = -0.100 +/- 0.026 s(-1), deltaR2 = -0.049 +/- 0.009 s(-1), and deltaf/f = 9.4 +/- 0.7% in the subcortical regions; and deltaR2* = -0.215 +/- 0.093 s(-1), deltaR2 = -0.069 +/- 0.012 s(-1), and deltaf/f = 16.2 +/- 1.2% in the cerebellar cortex.

Activity-based cost analysis: a method of analyzing the financial and operating performance of academic radiology departments.

PURPOSE: To develop a methodology for an activity-based cost (ABC) analysis in an academic radiology department, to test the hypothesis that the business of academic radiology can be separated into three distinct businesses-clinical activity, teaching, and research-and to determine the effect of the current teaching paradigm on clinical productivity. MATERIALS AND METHODS: Forty-seven key departmental activities were defined and distributed among the teaching, research, and clinical businesses. Individual radiologists determined the time spent in each of these activities by completing a detailed log of every activity performed during 2 weeks. All departmental revenue and costs were assigned to each activity in each of the three businesses. RESULTS: The methodology provided a successful understanding of the relative costs of each of the businesses of teaching, research, and clinical activity. It also provided the departmental costs of performing the separate activities typical of each business. Key findings included the following: Faculty spends 72% of time in clinical activities, research is the most expensive service per direct activity hour, and clinical reads (23%) are the single largest departmental cost element. CONCLUSION: ABC analysis can separate academic radiology into three businesses-teaching, research, and clinical-and provide a detailed understanding of the cost structure of each. This analysis identifies opportunities for improved quality of service, productivity, and cost within each business.

A crosslinguistic PET study of tone perception.

In studies of pitch processing, a fundamental question is whether shared neural mechanisms at higher cortical levels are engaged for pitch perception of linguistic and nonlinguistic auditory stimuli. Positron emission tomography (PET) was used in a crosslinguistic study to compare pitch processing in native speakers of two tone languages (that is, languages in which variations in pitch patterns are used to distinguish lexical meaning), Chinese and Thai, with those of English, a nontone language. Five subjects from each language group were scanned under three active tasks (tone, pitch, and consonant) that required focused-attention, speeded-response, auditory discrimination judgments, and one passive baseline as silence. Subjects were instructed to judge pitch patterns of Thai lexical tones in the tone condition; pitch patterns of nonspeech stimuli in the pitch condition; syllable-initial consonants in the consonant condition. Analysis was carried out by paired-image subtraction. When comparing the tone to the pitch task, only the Thai group showed significant activation in the left frontal operculum. Activation of the left frontal operculum in the Thai group suggests that phonological processing of suprasegmental as well as segmental units occurs in the vicinity of Broca's area. Baseline subtractions showed significant activation in the anterior insular region for the English and Chinese groups, but not Thai, providing further support for the existence of possibly two parallel, separate pathways projecting from the temporo-parietal to the frontal language area. More generally, these differential patterns of brain activation across language groups and tasks support the view that pitch patterns are processed at higher cortical levels in a top-down manner according to their linguistic function in a particular language.

Atrial fibrillation produced by prolonged rapid atrial pacing is associated with heterogeneous changes in atrial sympathetic innervation.

BACKGROUND: Structural and electrophysiological changes of the atria occur with prolonged rapid rates; however, the effects of sustained atrial fibrillation (AF) on autonomic innervation of the atria are unknown. We hypothesized that electrophysiological remodeling from rapid atrial rates is accompanied by altered atrial autonomic innervation. METHODS AND RESULTS: Six dogs (paced group) underwent atrial pacing at 600 bpm; 9 dogs (control animals) were not paced. All paced dogs developed sustained AF by week 4 of pacing. All 15 animals underwent positron emission tomography imaging of the atria with [C-11] hydroxyephedrine (HED) to label sympathetic nerve terminals. HED retention in the atria was significantly greater in paced dogs compared with control animals (P=0.03). Tissue samples from the atrial appendages had a greater concentration of norepinephrine in paced animals than in control animals (P=0.01). The coefficient of variation of HED retention was also greater in paced animals (P=0.05) and was greater in the right atrium than in the left atrium (P=0.004). Epicardial activation maps of AF were obtained in the paced animals at baseline and with autonomic manipulation. Mean AF cycle length was longer in the right atrium (109.2+/-5 ms) than in the left atrium (85.8+/-5.5 ms) at baseline (P=0.005). AF cycle length did not vary significantly from baseline (97.6+/-13.4 ms) with stellate stimulation (100.5+/-6 ms) but lengthened with propranolol (107.5+/-6.1 ms, P=0.03). CONCLUSIONS: Rapid rates of AF produce a heterogeneous increase in atrial sympathetic innervation. These changes parallel disparate effects of rapid pacing-induced AF on atrial electrophysiology.

PET imaging of cochlear-implant and normal-hearing subjects listening to speech and nonspeech.

Functional neuroimaging with positron emission tomography (PET) was used to compare the brain activation patterns of normal-hearing (NH) with postlingually deaf, cochlear-implant (CI) subjects listening to speech and nonspeech signals. The speech stimuli were derived from test batteries for assessing speech-perception performance of hearing-impaired subjects with different sensory aids. Subjects were scanned while passively listening to monaural (right ear) stimuli in five conditions: Silent Baseline, Word, Sentence, Time-reversed Sentence, and Multitalker Babble. Both groups showed bilateral activation in superior and middle temporal gyri to speech and backward speech. However, group differences were observed in the Sentence compared to Silence condition. CI subjects showed more activated foci in right temporal regions, where lateralized mechanisms for prosodic (pitch) processing have been well established; NH subjects showed a focus in the left inferior frontal gyrus (Brodmann's area 47), where semantic processing has been implicated. Multitalker Babble activated auditory temporal regions in the CI group only. Whereas NH listeners probably habituated to this multitalker babble, the CI listeners may be using a perceptual strategy that emphasizes 'coarse' coding to perceive this stimulus globally as speechlike. The group differences provide the first neuroimaging evidence suggesting that postlingually deaf CI and NH subjects may engage differing perceptual processing strategies under certain speech conditions.

Cardiac sympathetic denervation after transmyocardial laser revascularization.

BACKGROUND: Transmyocardial laser revascularization (TMR) has been shown to improve refractory angina not amenable to conventional coronary interventions. However, the mechanism of action remains controversial, because improved myocardial perfusion has not been consistently demonstrated. We hypothesized that TMR relieves angina by causing myocardial sympathetic denervation. METHODS AND RESULTS: PET imaging of resting and stress myocardial perfusion with [13N]ammonia (NH3) and of sympathetic innervation with [11C]hydroxyephedrine (HED) was performed before and after TMR in 8 patients with class IV angina ineligible for CABG or PTCA. A mean of 50+/-11 channels were created in the left ventricle (LV) with a holmium:YAG laser. A semiautomated program was used to determine NH3 uptake and HED retention in the LV. Perfusion and innervation defects were defined as the percentage of LV with tracer uptake or retention >2 SD below normal mean values. All patients experienced improvement in their angina by 2.4+/-0.5 angina classes after surgery, P=0.008. Sympathetic innervation defects exceeded resting perfusion defects in all patients before TMR (34.6+/-27.3% for HED versus 9.4+/-10.8% for NH3, P=0.008). TMR did not significantly affect resting or stress myocardial perfusion but increased the extent of sympathetic denervation in 6 of 8 patients by 27.5+/-15.9%, P=0.03. In the remaining 2 patients, both sympathetic denervation and stress perfusion defects decreased after surgery. CONCLUSIONS: TMR causes decreased myocardial HED uptake in most patients without significant change in resting or stress myocardial perfusion, suggesting that the improvement in angina may be at least in part due to sympathetic denervation.

PET imaging of oxidative metabolism abnormalities in sympathetically denervated canine myocardium.

UNLABELLED: This study was designed to test the hypothesis that regional sympathetic denervation produces perfusion and metabolic alterations in myocardial tissue under resting conditions. METHODS: PET studies of myocardial sympathetic innervation, myocardial perfusion and oxygen utilization using [11C]hydroxyephedrine (HED), [13N]ammonia and 1-[11C]acetate, respectively, were performed before and approximately 2 and 8 wk after surgical left thoracotomy and regional chemical sympathetic denervation (n = 5). A second group of animals underwent the same surgical procedure but, so that they could serve as a sham control group, were not sympathetically denervated (n = 5). The second group of animals was imaged before and 2 wk after surgery. Images of the retention of [11C]HED taken from 50 to 60 min postinjection were used to differentiate sympathetically innervated and denervated regions of the left ventricle. Regions of interest were defined on polar plots of the [11C]HED retention, including the sympathetically denervated territory and normally innervated regions. Regions defined on the HED polar plots were then transferred to the [13N]ammonia and 1-[11C]acetate image data, and tracer kinetic models were fit to the regional time-activity curves to generate estimates of myocardial perfusion and oxidative metabolism. RESULTS: The average percentage of the left ventricle denervated in the group I animals was 13.1% +/- 7.3%. Significant reductions in oxidative metabolism were observed in the sympathectomized tissue both at 2 and 8 wk after surgery (22% and 15% reductions, respectively). Significant alterations in regional perfusion were not observed. No significant changes in oxidative metabolism or perfusion were observed in the sham control group. CONCLUSION: Regional sympathetic denervation alters oxidative metabolism but not perfusion in the denervated region of the heart.

Presurgical evaluation and surgical outcome of temporal lobe epilepsy.

The authors analyzed 22 patients younger than 18 years of age with temporal lobe epilepsy (TLE) treated surgically. Patients underwent a comprehensive presurgical evaluation, including video-electroencephalogram. Fifty-five percent had a history of febrile seizures. Eighty-two percent had auraes and most exhibited oroalimentary and gestural automatisms. Contralateral dystonic posturing was present in 36% and postictal dysphasia in 54% of patients with left-sided resections. Cranial magnetic resonance imaging (MRI) was abnormal in 59% of patients. MRI revealed changes consistent with mesial temporal sclerosis in 8 (47%) of 17 patients without lesions. Fluorodeoxyglucose-positron emission tomography (PET) scans revealed ipsilateral temporal hypometabolism (PET-TH) in 12 (85.7%) of 14 patients. The intracarotid amobarbital procedure revealed impaired memory of the epileptogenic side in 59% of patients. Seventeen patients underwent en-bloc resections and five lesionectomies and resection of the epileptogenic area. There was no surgical morbidity or mortality. Forty-three percent had hippocampal sclerosis, 28.5% gliosis, 14% low-grade tumors, 9.5% cavernous angiomas, and 5% had no pathologic findings. Follow-up (6 months to 12 years) was available for 21 patients; 76% became seizure free, 19% had rare seizures, and 5% had a worthwhile improvement. TLE can be safely treated surgically in younger patients with excellent results. The clinical manifestations were similar to adult patients. PET-TH was present even at a younger age, suggesting that the focal functional deficits appear early in patients with medically refractory TLE, which may help in the early identification of these patients.

PET imaging of the pre-synaptic dopamine uptake sites in rapid-onset dystonia-parkinsonism (RDP).

BACKGROUND: Rapid-onset dystonia-parkinsonism (RDP) is a genetic movement disorder characterized by abrupt onset over hours to days of bradykinesia, postural instability, dysphagia, dysarthria, and severe dystonic spasms with decreased levels of the dopamine metabolite, homovanillic acid (HVA), in cerebrospinal fluid (CSF). METHODS: We imaged the dopamine re-uptake system with [O-methyl-11C]beta-CFT ([11C]beta-CFT) in three severely affected individuals with RDP and four patients with idiopathic Parkinson's disease (IPD). Results were compared with those of age-matched normal volunteers. RESULTS: Positron emission tomography images from those patients with IPD demonstrated a dramatic reduction in the volume of distribution of [11C]beta-CFT whereas patients with RDP showed slightly elevated values. CONCLUSIONS: The data suggest that patients with RDP do not have a decrease in the number of dopamine re-uptake sites. Our findings suggest that, unlike the situation in IPD, low CSF HVA concentrations seen in RDP patients are not the result of degeneration of striatal dopamine terminals or loss of dopamine re-uptake sites.

Functional brain imaging in apraxia.

BACKGROUND: An extensive literature describes structural lesions in apraxia, but few studies have used functional neuroimaging. We used positron emission tomography (PET) to characterize relative cerebral glucose metabolism in a 65-year-old, right-handed woman with progressive decline in ability to manipulate objects, write, and articulate speech. OBJECTIVE: To characterize functional brain organization in apraxia. DESIGN AND METHODS: The patient underwent a neurological examination, neuropsychological testing, magnetic resonance imaging, and fludeoxyglucose F 18 PET. The patient's magnetic resonance image was coregistered to her PET image, which was compared with the PET images of 7 right-handed, healthy controls. Hemispheric regions of interest were normalized by calcrine cortex. RESULTS: Except for apraxia and mild grip weakness, results of the neurological examination were normal. There was ideomotor apraxia of both hands (command, imitation, and object) and buccofacial apraxia. The patient could recognize meaningful gestures performed by the examiner and discriminate between his accurate and awkward pantomime. The magnetic resonance image showed moderate generalized atrophy and mild ischemic changes. Positron emission tomographic scans showed abnormal fludeoxyglucose F 18 uptake in the posterior frontal, supplementary motor, and parietal regions, the left affected more than the right. Focal metabolic deficit was present in the angular gyrus, an area hypothesized to store conceptual knowledge of skilled movement. CONCLUSIONS: Greater parietal than frontal physiological dysfunction and preserved gesture recognition are not consistent with the theory that knowledge of limb praxis is stored in the dominant parietal cortex. Gesture comprehension may be more diffusely distributed.