Evaluation of cannabinoid type 1 receptor expression in the rat brain using [¹8F]MK-9470 microPET.

PURPOSE: The ligand [(18)F]MK-9470 is an inverse agonist binding with high affinity and specificity to the cannabinoid type 1 (CB1) receptor. In this study, a semiquantitative acquisition and analysis protocol for investigation of the CB1 receptor distribution in the rat brain was established. METHODS: Two C57BL/6N mice (one CB1 (-/-) and one wild-type) and 19 Sprague Dawley rats were investigated using a Focus 120 microPET scanner. Seven rats were scanned twice for test-retest evaluation, six rats were scanned for blocking experiments using the inverse CB1 receptor agonist rimonabant, and 19 rats were scanned for baseline studies. Percentage injected dose per millilitre (%ID/ml) or uptake ratios (VOItarget/VOIwhole brain) were calculated. A Bland-Altman-plot was computed and mean values were compared using a two-sided paired t test. RESULTS: Comparing the data from the CB1 (-/-) mouse and the wild-type mouse, [(18)F]MK-9470 showed good specificity. Regarding the rat data, there was no relationship between the difference between the test and retest measurements or their mean value. The test and retest data showed a strong correlation (ρ c = 0.846, p ≤ 0.01; r Pearson = 0.857). Equivalence was not found for all regions and not even in the pons at baseline or under blocking condition. Only the baseline studies showed the highest levels of uptake in the caudate-putamen and thalamus, whereas moderate uptake was found in the hippocampus, hypothalamus and cerebellum, and the lowest uptake was observed in the cortex, amygdala and pons. CONCLUSION: A reference region is not available; however, the proposed analysis method using the parameter uptake ratio is simple and delivers stable results allowing the discrimination of distinct brain regions.

PET lung ventilation/perfusion imaging using (68)Ga aerosol (Galligas) and (68)Ga-labeled macroaggregated albumin.

Pulmonary imaging using ventilation/perfusion (V/P) single-photon emission tomography (V/P scan) with Tc-99m-labeled radiotracers is a well-established diagnostic tool for clinically suspected pulmonary embolism (PE). Ga-68 aerosol (Galligas) and Ga-68-labeled macroaggregated albumin (MAA) are potential tracers for positron emission tomography (PET) lung V/P imaging and could display an advantage over conventional V/P scans in terms of sensitivity and specificity. After radiochemical and animal studies, the clinical applicability of Ga-68 aerosol (Galligas) and Ga-68-labeled MAA was investigated in an exploratory study in patients with clinical suspicion of PE. PET scans were acquired using a 16-slice Gemini TF positron emission tomography/computed tomography (PET/CT) scanner. The acquisition protocol included low-dose computed tomography (CT) for attenuation correction (AC). Dosimetry calculations and continuative phantom measurements were performed. Structural analyses showed no modification of the particles due to the labeling process. In addition, in vitro experiments showed stability of Ga-68 MAA in various media. As expected, Ga-68-labeled human serum albumin microspheres (HSAM) were completely retained in the lung of the animals. In clinical use, PET lung ventilation and perfusion imaging using Ga-68 aerosol (Galligas) and Ga-68-labeled MAA was successful in all cases. In one case a clinically suspected PE could be detected and verified. The administered activity of Ga-68 aerosol (Galligas) and Ga-68-labeled MAA may be reduced by more than 50%, resulting in comparable radiation exposure to conventional V/P scans. In conclusion, Ga-68 aerosol (Galligas) and Ga-68-labeled MAA are efficient substitutes for clinical use and could be an interesting alternative with high accuracy for lung V/P imaging with Tc-99m-labeled radiotracers, especially in times of Mo-99 shortages and increasing use and spread of PET/CT scanners and Ga-68 generators, respectively.

[German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids]. / PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren.

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.

Cortical control of thermoregulatory sympathetic activation.

Thermoregulation enables adaptation to different ambient temperatures. A complex network of central autonomic centres may be involved. In contrast to the brainstem, the role of the cortex has not been clearly evaluated. This study was therefore designed to address cerebral function during a whole thermoregulatory cycle (cold, neutral and warm stimulation) using 18-fluordeoxyglucose-PET (FDG-PET). Sympathetic activation parameters were co-registered. Ten healthy male volunteers were examined three times on three different days in a water-perfused whole-body suit. After a baseline period (32 degrees C), temperature was either decreased to 7 degrees C (cold), increased to 50 degrees C (warm) or kept constant (32 degrees C, neutral), thereafter the PET examination was performed. Cerebral glucose metabolism was increased in infrapontine brainstem and cerebellar hemispheres during cooling and warming, each compared with neutral temperature. Simultaneously, FDG uptake decreased in the bilateral anterior/mid-cingulate cortex during warming, and in the right insula during cooling and warming. Conjunction analyses revealed that right insular deactivation and brainstem activation appeared both during cold and warm stimulation. Metabolic connectivity analyses revealed positive correlations between the cortical activations, and negative correlations between these cortical areas and brainstem/cerebellar regions. Heart rate changes negatively correlated with glucose metabolism in the anterior cingulate cortex and in the middle frontal gyrus/dorsolateral prefrontal cortex, and changes of sweating with glucose metabolism in the posterior cingulate cortex. In summary, these results suggest that the cerebral cortex exerts an inhibitory control on autonomic centres located in the brainstem or cerebellum. These findings may represent reasonable explanations for sympathetic hyperactivity, which occurs, for example, after hemispheric stroke.

Hyperechogenicity of the substantia nigra in healthy controls is related to MRI changes and to neuronal loss as determined by F-Dopa PET.

Transcranial ultrasound (TCS) has been shown to reveal hyperechogenicity of the substantia nigra (SN) in Parkinsonian patients and in about 10% of healthy controls. It is hypothesized that SN hyperechogenicity in healthy subjects is a vulnerability marker for idiopathic Parkinson's disease (IPD). Although there is strong evidence that the echomarker results from increased local iron content, the exact pathophysiological mechanisms remain incompletely understood. Thus, prognostic impact can only be estimated. We examined 14 subjects with SN hyperechogenicity (SN+) (7 IPD patients and 7 controls) and 7 healthy controls without the echomarker (SN-) by a magnetic resonance imaging method (MRI; T2 relaxation times) known to reveal tissue inhomogeneity following abnormal iron content and by F-Dopa PET to assess nigrostriatal function.

Laparoscopic radioisotope-guided sentinel lymph node mapping and excision of the rectum--an experimental study.

BACKGROUND: Patients with a low-risk T1 rectal carcinoma can undergo the therapy of a local excision. In these patients the lymph node (LN) status remains unknown. There is a potential risk of up to 7% for nodal metastasis. To investigate the possibility of using the sentinel lymph node (SLN) concept, an experimental study on pigs was undertaken. The objective was to laparoscopically identify and extract SLNs from the rectum using a radioisotope (RI). METHODS: The experiment was conducted in 30 pigs, since the sample size calculation indicated that with 30 animals a two-sided 95% confidence interval for a single proportion using the large sample normal approximation would extend at most 0.107 from the observed proportion of 0.9. One milliliter of a mixture of the RI Technetium 99 m (Tc99 m) and patent blue V dye was administered in the rectum endoscopically and after the lapse of 1 h, we laparoscopically identified and excised all SLNs using a laparoscopic gamma camera probe. RESULTS: We found in all operated pigs (n = 30) at least one SLN (lymph node with highest measured counts per second (cps)). In mean we detected 1.6 SLN (range one to three SLNs). In 28 cases, the SLN concept was successful. Sensitivity for detecting SLNs was 93% (n = 28/30), the probe count rate ranged from 600-10,000 cps with a median of 3,800. CONCLUSION: Minimal invasive mapping and excision of SLN of the rectum using a RI is feasible. The sensitivity for detecting SLN was high (93%). The application of this procedure on humans seems to be possible.

Whole-body biodistribution of the cannabinoid type 1 receptor ligand [18F]MK-9470 in the rat.

The endocannabinoid system participates in many processes in the body, including memory, reward, pain, motor activity, food intake, energy metabolism, and gastrointestinal functions. [18F]MK-9470 is a positron emission tomography (PET) ligand that binds with high affinity and selectivity to the cannabinoid type 1 receptor. In order to fully characterize ligand behavior, tracer uptake measured using in vivo microPET was compared with results from ex vivo tissue dissection. Twelve male Sprague-Dawley rats were divided into three subgroups and scanned over time periods of 10min, 30min and 90min using PET. Afterwards, a number of the animals' organs were dissected. Uptake of radioactivity was expressed in terms of %ID/ml and %ID/(g tissue). For comparison of in vivo and ex vivo methods, Bland-Altman plots were computed. The highest uptake of [18F]MK-9470 was found in the liver and small intestine; the brain showed less uptake, while low and unspecific binding was observed in tissue of the heart, lung, kidney and bone. In the brain, normalized uptake of [18F]MK-9470 was on average 0.25%ID/ml (range: 0.16 to 0.28%ID/ml). Bland-Altman plots revealed the best agreement between methods for the 90min acquisition protocols. High hepatic accumulation and metabolism of [18F]MK-9470 occur with mainly enteral excretion, which may vary considerably over time - a finding which may be of relevance in metabolite determination in quantitative brain studies. Comparisons between in vivo and ex vivo methods showed that whole-body distribution of [18F]MK-9470 using positron emission tomography is a preferable alternative to ex vivo biodistribution, and requires a significantly smaller number of animals.

Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

Δ9-Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [18F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of < 1 ng/ml (injected dose: ≤ 0.01 mg/kg) corresponded to an increased glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies.

Positron emission tomography reveals correlations between brain metabolism and mood changes in hyperthyroidism.

CONTEXT: Hyperthyroidism is frequently associated with emotional distress. The underlying cerebral processes of the endocrine-induced mood changes are unclear. OBJECTIVE: The objective of this study was to investigate, for the first time, the neuronal correlates of thyrotoxicosis-associated psychic symptoms using positron emission tomography (PET). DESIGN: The study was designed as a cross-sectional trial. SETTING: The study was performed at joint nuclear medicine and thyroid clinics. PATIENTS: Twelve patients with untreated Graves' hyperthyroidism were evaluated. METHODS: Levels of emotional distress were self-rated by means of the Hospital Anxiety and Depression Scale. Both patients and 20 age- and gender-matched euthyroid controls underwent a brain fluorodeoxyglucose PET scan. Subsequently, the functional relationship between brain metabolism and the psychometric scores was analyzed. RESULTS: Compared with controls and visualized by fluorodeoxyglucose PET, hyperthyroid patients showed a decreased (P < 0.0001) glucose metabolism in the limbic system (uncus and inferior temporal gyrus). Activation foci in the posterior cingulate and in the inferior parietal lobe were correlated with both anxiety and depression scales (P < 0.001). Compared with patients with normal anxiety levels, those with increased anxiety yielded an enhanced glucose metabolism (P < 0.001) in the bilateral sensory association cortex. Serum free T3/free T4 levels negatively correlated with regional glucose metabolism in the medial posterior cingulate. CONCLUSIONS: Thyrotoxicosis and associated psychic symptoms are correlated to regional metabolic changes in the main structures of the limbic/paralimbic system.

FDG-PET in the initial staging of squamous cell oesophageal carcinoma.

UNLABELLED: Squamous cell oesophageal carcinoma is the most common carcinoma of the oesophagus worldwide. The tumour stage as most important prognostic factor determines the clinical management. AIM: of this study was to evaluate the value of FDG-PET 1. in imaging the primary tumour and 2. in N- and M-staging of squamous cell oesophageal carcinoma. PATIENTS, METHODS: In 20 patients with histological proven squamous cell carcinoma of the upper and middle oesophagus, FDG-PET was performed in standard technique prior to therapy. FDG uptake in the primary was determined by calculation of the SUVmax. NM-staging due to PET findings was performed as designated by the AJCC/UICC group classification and was compared with pathological and clinically based staging. Sensitivities, specificities and accuracies were calculated. RESULTS: In 19 of 20 patients, primary squamous cell oesopohageal carcinoma was detected by FDG-PET findings with a maximum SUV of 12.5 (mean) +/- 5.1 (median 11.5; range 4.8-23.8). One carcinoma in situ was missed. The sensitivity of FDG-PET in imaging the primary tumour was 96%. The sensitivities, specificities and accuracies were 20%, 100%, 58% for N-staging, and 60%, 86% and 93% for M-staging. PET findings caused changes of therapy in 5% (1 patient). CONCLUSIONS: FDG-PET was excellent in imaging the primary of squamous cell oesophageal carcinoma in stage T1-T4 and was efficient in M-staging. The low sensitivity in N-staging is of inferior clinical importance. The efficacy of FDG-PET seems to be not significantly be influenced by the histological subtype of oesophageal carcinoma.

Primary non-refluxive megaureter in children: single-center experience and follow-up of 212 patients.

PURPOSE: Primary non-refluxing megaureter (pMU) is a multifaceted and challenging congenital pathology of the urinary tract. We report our 23-year experience with this anomaly in terms of presentation, diagnostic work-up and management. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 212 children diagnosed with pMU between 1986 and 2009 at our institution. Mean follow-up was 45.17 (0-192) months. RESULTS: Of the total, 168 (79 %) children presented with upper urinary tract dilation on perinatal ultrasound screening. In 44 (21 %) patients, the diagnosis was made following diagnostic work-up of a urinary tract infection (UTI, 18 %) or flank pain (3 %). In total, 203 of 254 pMUs (79.9 %) were successfully treated conservatively during the 23-year observation period. Forty-eight children (23 %) underwent ureteric reimplantation. UTIs occurred in 91 of 212 children (43 %). Of these, 41 (45 %) occurred despite antibacterial infection prophylaxis. Within the past three decades, there has been a marked shift from surgical toward conservative therapy at our institution. CONCLUSION: Neonatal renal ultrasound is the method of choice to timely identify children with pMU and, alongside dynamic renography, to monitor the clinical course. Nowadays, only a minor subset of children with asymptomatic course requires surgical correction. Antibacterial prophylaxis has the potential to reduce the risk of febrile UTIs. Prospective randomized studies are warranted to provide evidence of the beneficial effect of antibacterial prophylaxis.

In vitro and in vivo evaluation of novel glibenclamide derivatives as imaging agents for the non-invasive assessment of the pancreatic islet cell mass in animals and humans.

Pancreatic islet cell mass (PICM) is a major determinant of the insulin secretory capacity in humans. Currently, the only method for accurate assessment of the PICM is an autopsy study. Thus, development of a technique allowing the non-invasive quantification of PICM is of great interest. The aim of this study was to develop such a non-invasive technique featuring novel fluorine- and (99m)Tc-labelled glibenclamide derivatives. Despite the structural modifications necessary to introduce fluorine into the glibenclamide molecule, all derivatives retained insulin stimulating capacity as well as high affinity binding to human SUR1 when compared to the original glibenclamide. Contrastingly, the lipophilicity of the fluorine-labelled derivatives was altered depending on the particular modification. In the human PET-study a constant but weak radioactive signal could be detected in the pancreas using a fluorine-labelled glibenclamide derivative. However, a reliable assessment and visualisation of the PICM could not be obtained. It can be assumed that the high uptake of the fluorine-labelled tracer e.g. into the the liver and the high plasma protein binding leads to a relatively low signal-to-noise ratio. In case of the presented fluorine-labelled glibenclamide based compounds this could be the result of their invariably high lipophilicity. The development of a (99 m)Tc-labelled glibenclamide derivative with a lower lipophilicity and differing in vivo behaviour, glibenclamide based compounds for non-invasive imaging of the pancreatic islet cell mass may be possible.

Haematopoietic toxicity of radium-223 in patients with high skeletal tumour burden.

UNLABELLED: In patients with metastasized, castration resistant prostate cancer (mCRPC) treatment with radium-223 (Xofigo) is an attractive therapeutic option. In particular, patients with high tumour load seem to profit from this treatment in regard of survival and quality of live. Aim of this study was to stratify mCRPC patients according to a quantitative imaging marker derived from routine bone scans (EXINI bone) and analyze haematopoietic toxicity of Xofigo in these patients. PATIENTS, METHODS: Toxicity and oncologic outcome were investigated in a cohort of 14 patients with high tumour load. Additionally, based on a web survey, experience of toxicity in 41 high tumour load patients in Germany in 2014 was collected. RESULTS: In patients with a bone scan index (BSI) greater than 5, significant toxicity occurred in more patients than expected from the ALSYMPCA trial. This was associated with application of fewer cycles. Similar experiences have been made in other centers in Germany. Approximately 7% of these patients will need very long time or will not recover from grade ≥ 3 toxicity. CONCLUSION: Close follow-up of haematopoietic indices and, in case of toxicity, early termination of therapy is in particular necessary in late stage disease where limited bone marrow reserve is likely.

Success rate of radioiodine therapy in Graves' disease: the influence of thyrostatic medication.

There is controversy whether simultaneous thyrostatic medication influences the outcome of radioiodine (131I) therapy in Graves' disease by reducing the absorbed energy dose of 131I when delivering a standard dose. We therefore sought to ascertain whether the outcome of ablative 131I therapy is in any way affected by simultaneous thyrostasis (carbimazole) by aiming for a constant absorbed dose of 200-250 Gy. We prospectively studied 207 patients with Graves' disease (106 with and 101 without simultaneous carbimazole at the time of 131I therapy). All patients were reexamined 3, 6, and 12 months after 131I therapy. The 101 nonthyrostatic patients showed a highly significantly greater success rate (93%) than the 106 thyrostatic patients (49%). Stepwise logistic regression demonstrated that failure was related to the administration of carbimazole during 131I therapy (P < 0.00005) and the absorbed dose (P < 0.025), but was not related to free T3, free T4, TSH receptor antibodies, or thyroid volume. The success rate was 100% in 93 nonthyrostatic patients with absorbed doses of 200 Gy or more, but was only 12.5% (1 of 8) for absorbed doses less than 200 Gy. Correlation between success and absorbed dose was significantly higher for nonthyrostatic than for thyrostatic patients (r = 0.93 vs. r = 0.24). Sixteen patients who discontinued thyrostasis 1-3 days before 131I therapy showed 94% successes. Simultaneous thyrostasis is the decisive factor against a successful 131I therapy even if the significantly reduced 131I uptake/half-life values under thyrostasis are compensated with a higher delivered dose to ensure a comparable absorbed dose, possibly due to the additionally effective radioprotective properties of carbimazole. Therefore, if clinically feasible, we recommend discontinuing thyrostasis at least 1 day before beginning 131I therapy, because even in hyperthyroid nonthyrostatic patients the success rate was 100%.

Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG.

The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation word association) within 2-4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens.

Regional cerebral blood flow and negative/positive symptoms in 24 drug-naive schizophrenics.

UNLABELLED: SPECT/PET studies in schizophrenia revealed inconsistent changes of regional cerebral blood flow (rCBF). Frontal hyperperfusion as well as hypoperfusion are described. This study was undertaken to investigate the relations between rCBF, psychopathology according to PANSS and effects of neuroleptic therapy. METHODS: Twenty-four drug-naive acute patients with a first manifestation of schizophrenia were examined with 99mTc-HMPAO brain SPECT and assessed according to PANSS. Of these, 22 were controlled again after neuroleptic treatment. Following attenuation correction, region-to-cerebellar count ratios were obtained from 98 irregular regions of interest drawn in all slices (6.25 mm). The ratios were compared to 20 control subjects, and changes lying outside of 2 s.d. were considered abnormal. RESULTS: In different drug-naive patients, hyperperfusion as well as hypoperfused patterns were found. In drug-naive patients, the seven subscores of positive symptoms (pos 1-7) in PANSS showed different correlations to rCBF: Formal thought disorders (pos 2) and grandiosity (pos 5) were positively correlated to bifrontal and bitemporal rCBF (r = +0.59 to +0.70). Delusional ideas (pos 1), hallucinatory behavior (pos 3) and suspiciousness (pos 6) demonstrated a negative correlation to bifrontal, cingulate, left temporal and left thalamic rCBF (r = -0.59 to -0.66). Stereotyped ideas (neg 7) as a negative symptom showed a negative correlation to left frontal, left temporal and left parietal rCBF (r = -0.59 to -0.65). No correlations were found between residual positive symptoms and rCBF after neuroleptic treatment and clinical improvement, but all negative symptoms (neg 1-7) had a negative correlation to bifrontal, bitemporal, cingulate, basal ganglia and thalamic rCBF (r = -0.59 to -0.74). CONCLUSION: Our results illustrate that different positive symptoms are accompanied by different rCBF values: some induce hyperperfusion, others hypoperfusion. After therapy (and reduction of positive symptoms), only negative symptoms correlate exclusively to hypoperfusion. This may be the crucial factor in explaining inconsistencies of past results in perfusion pattern in drug-naive schizophrenic patients.

Correlation of neuropsychological, morphological and functional (regional cerebral blood flow and glucose utilization) findings in cerebral microangiopathy.

UNLABELLED: Cerebral microangiopathy, indicated in MRI by lacunar infarctions (LIs) and deep white matter lesions (DWMLs), is said to be accompanied by vascular dementia, which is reportedly caused by LI and DWML. METHODS: To confirm this assumption, 57 patients with cerebral microangiopathy were assessed for changes in regional cerebral blood flow (rCBF) and glucose utilization (rMRGlu) in both white matter and cortex, and these findings were correlated to the results of extensive neuropsychological testing (cognitive, mnestic and attentiveness tests), as well as to MRI findings. A special head holder ensured reproducibility of positioning during measurement of rCBF (99mTc-HMPAO SPECT) and rMRGlu (18F-FDG PET) and MRI. White matter and cortex were quantified with regions of interest defined on MRI and superimposed to corresponding PET/SPECT slices. The rMRGlu was calculated according to Sokoloff, and rCBF was determined from normalization to the cerebellum. LI and DWML were graded by number and extent. Brain atrophy was classified as no to slight inner and/or outer atrophy (Group A) or moderate-to-severe inner and outer atrophy (Group B). RESULTS: Even in severe DWMLs and in multiple LIs, rCBFs and rMRGlu values were not reduced. Analysis of variance identified atrophy and neuropsychological deficits as the main determinants for reduced rCBF and rMRGlu values (p < 0.05). However, 60% of patients (19 of 31) with neuropsychological deficits in attentiveness tests and 61% of patients (23 of 38) with mnestic deficits belonged to Group A and revealed decreased rCBF and rMRGlu values. Neuropsychological deficits correlated well with decreased rCBF and rMRGlu, whereas MRI patterns, such as LI and DWML, did not. CONCLUSION: We conclude that LI and DWML are epiphenomena that morphologically characterize cerebral microangiopathy. Dementia or neuropsychological deficits, however, are exclusively reflected by functional criteria (rCBF and rMRGlu), as long as cerebral atrophy does not occur.

Radioiodine therapy in Graves' disease patients with large diffuse goiters treated with or without carbimazole at the time of radioiodine therapy.

We sought to ascertain how high the success rates of radioiodine therapy are for Graves' disease patients with large diffuse goiters when aiming for a constant absorbed dose of 250 Gy. Thirty-six patients with a thyroid volume of 50-110 mL were evaluated for changes in thyroid function and appearance 3, 6, and 12 months after radioiodine therapy. Success was defined as definitive elimination of hyperthyroidism following therapy (hypothyroidism corrected with thyroxine on diagnosis); failure as persistent/recurrent hyperthyroidism after 12 months. Overall success rate was 50%. However, a subgroup of 20 patients without simultaneous carbimazole (carbimazole-off) showed a highly significantly larger success rate (85%) than the 16 patients with simultaneous carbimazole (carbimazole-on) at the time of radioiodine therapy (6.3%, p < 0.000005). Successful cases showed a significantly higher volume reduction after radioiodine than failures (75.5% vs. 35.4%, p < 0.00005). Stepwise logistic regression showed that therapy failure was related to administration of carbimazole during radioiodine therapy (p < 0.0250 and absorbed dose (p < 0.05), but not thyroid function (free triiodothyronine [FT3] and free thyroxine [FT4]), initial thyroid volume or thyrotropin-receptor antibody (TRAb) value. However, a significant correlation of therapy success to absorbed dose (r = 0.69, p < 0.005) could be shown only for carbimazole-off patients, but not for the others. Finally, multivariate factor analysis consistently showed that therapy success was correlated only to absorbed dose and antithyroid drugs, not to initial thyroid volume, TRAb value, or thyroid function. Thyroid volume per se is not responsible for the lower success rate in Graves' disease patients with large goiters because even a comparable group of 32 Graves' disease patients with small thyroid glands (< or =20 mL) and without simultaneous carbimazole showed a success rate of 87.5%. The high failure rate in the carbimazole-on patients (absorbed dose comparable to carbimazole-off) is due to the simultaneous administration of carbimazole. Therefore, if clinically feasible, we recommend discontinuing carbimazole at least one day before beginning radioiodine therapy.