The Possible Link between GABAergic Dysfunction and Cognitive Decline in a Patient with Idiopathic Hypoparathyroidism.

Idiopathic hypoparathyroidism (IHP) is accompanied by cognitive impairment. We report the case of a 70-year-old IHP patient with cognitive disturbance. Brain computed tomography showed bilateral calcification in basal ganglia, thalamus, and cerebellum. Neuropsychological assessment revealed low scores for intelligence, memory, and perseverative errors. Brain positron emission tomography showed a significant reduction in [(18)F]-Fludeoxyglucose (FDG) uptake in bilateral frontal, left temporal and parietal cortices, along with a marked reduction in [(11)C]-flumazenil binding in left frontal, temporal, parietal, and bilateral cerebellum. These findings suggest cognitive impairment in IHP may be ascribed to GABAergic dysfunction, thus leading to, or coexisting with, cerebral hypometabolism.

Alterations in α4ß2 nicotinic receptors in cognitive decline in Alzheimer's aetiopathology.

Nicotinic acetylcholine receptor subtype α4ß2 is considered important in the regulation of attention and memory, and cholinergic degeneration is known as one pathophysiology of Alzheimer's disease. Brain amyloid-ß protein deposition is also a key pathological marker of Alzheimer's disease. Recent amyloid-ß imaging has shown many cognitively normal subjects with amyloid-ß deposits, indicating a missing link between amyloid-ß deposition and cognitive decline. To date, the relationship between the α4ß2 nicotinic acetylcholine receptor and amyloid-ß burden has not been elucidated in vivo. In this study we investigated the relation between α4ß2 nicotinic acetylcholine receptor availability in the brain, cognitive functions and amyloid-ß burden in 20 non-smoking patients with Alzheimer's disease at an early stage and 25 age-matched non-smoking healthy elderly adults by measuring levels of α4ß2 nicotinic acetylcholine receptor binding estimated from a simplified ratio method (BPRI) and Logan plot-based amyloid-ß accumulation (BPND) using positron emission tomography with α4ß2 nicotinic acetylcholine receptor tracer (18)F-2FA-85380 and (11)C-Pittsburgh compound B. The levels of tracer binding were compared with clinical measures for various brain functions (general cognition, episodic and spatial memory, execution, judgement, emotion) using regions of interest and statistical parametric mapping analyses. Between-group statistical parametric mapping analysis showed a significant reduction in (18)F-2FA-85380 BPRI in the cholinergic projection region in patients with Alzheimer's disease with a variety of (11)C-Pittsburgh compound B accumulation. Spearman rank correlation analyses showed positive correlations of (18)F-2FA-85380 BPRI values in the medial frontal cortex and nucleus basalis magnocellularis region with scores of the Frontal Assessment Battery (a test battery for executive functions and judgement) in the Alzheimer's disease group (P < 0.05 corrected for multiple comparison), and also positive correlations of the prefrontal and superior parietal (18)F-2FA-85380 BPRI values with the Frontal Assessment Battery score in the normal group (P < 0.05 corrected for multiple comparison). These positive correlations indicated an in vivo α4ß2 nicotinic acetylcholine receptor role in those specific functions that may be different from memory. Both region of interest-based and voxelwise regression analyses showed a negative correlation between frontal (11)C-Pittsburgh compound B BPND and (18)F-2FA-85380 BPRI values in the medial frontal cortex and nucleus basalis magnocellularis region in patients with Alzheimer's disease (P < 0.05 corrected for multiple comparison). These findings suggest that an impairment of the cholinergic α4ß2 nicotinic acetylcholine receptor system with the greater amount of amyloid deposition in the system plays an important role in the pathophysiology of Alzheimer's disease.

Reduction of [11C](+)3-MPB binding in brain of chronic fatigue syndrome with serum autoantibody against muscarinic cholinergic receptor.

BACKGROUND: Numerous associations between brain-reactive antibodies and neurological or psychiatric symptoms have been proposed. Serum autoantibody against the muscarinic cholinergic receptor (mAChR) was increased in some patients with chronic fatigue syndrome (CFS) or psychiatric disease. We examined whether serum autoantibody against mAChR affected the central cholinergic system by measuring brain mAChR binding and acetylcholinesterase activity using positron emission tomography (PET) in CFS patients with positive [CFS(+)] and negative [CFS(-)] autoantibodies. METHODOLOGY: Five CFS(+) and six CFS(-) patients, as well as 11 normal control subjects underwent a series of PET measurements with N-[(11)C]methyl-3-piperidyl benzilate [(11)C](+)3-MPB for the mAChR binding and N-[(11)C]methyl-4-piperidyl acetate [(11)C]MP4A for acetylcholinesterase activity. Cognitive function of all subjects was assessed by neuropsychological tests. Although the brain [(11)C](+)3-MPB binding in CFS(-) patients did not differ from normal controls, CFS(+) patients showed significantly lower [(11)C](+)3-MPB binding than CFS(-) patients and normal controls. In contrast, the [(11)C]MP4A index showed no significant differences among these three groups. Neuropsychological measures were similar among groups. CONCLUSION: The present results demonstrate that serum autoantibody against the mAChR can affect the brain mAChR without altering acetylcholinesterase activity and cognitive functions in CFS patients.

Single 20-second acquisition of deep-inspiration breath-hold PET/CT: clinical feasibility for lung cancer.

UNLABELLED: This study was designed to compare tumor (18)F-FDG uptake between a single 20-s acquisition of deep-inspiration breath-hold PET/CT and free-breathing PET/CT for lung cancer. METHODS: Before the clinical study, a phantom study was performed to determine the optimum breath-hold time for the PET scan. We studied 47 patients with lung cancer who underwent free-breathing PET/CT with the standard clinical protocol, followed by deep-inspiration breath-hold PET/CT of the thorax. In breath-hold PET/CT, the patients were asked to hold their breath in deep inspiration for 10 s during the CT scan and for 20 s during the PET scan. Maximum tumor (18)F-FDG standardized uptake value (SUVmax) was measured in free-breathing PET and breath-hold PET, and the percentage difference between these 2 values was calculated. RESULTS: Breath-hold PET showed a significant increase in SUVmax, as compared with free-breathing PET (8.26 +/- 4.59 vs. 11.25 +/- 7.24, P < 0.0001). The mean difference in SUVmax was 39.5% +/- 43.4%, and the range was 2.9%-248.3%. The difference in SUVmax was significant when compared between tumors in the upper lung (n = 22) and tumors in the lower lung (n = 25) (24.4% +/- 17.7% vs. 52.9% +/- 54.3%, P = 0.0077). The mean tumor size of the group with a high SUVmax difference (n = 13) was significantly smaller than that of the group with a low SUVmax difference (n = 34) (2.45 +/- 0.87 cm vs. 3.21 +/- 1.22 cm, P = 0.043), using a cutoff of 39.5%. CONCLUSION: The single 20-s acquisition of breath-hold PET/CT enabled more precise measurement of SUVmax, especially in the lower lung field and for small tumors, which may be affected by respiratory motion. This technique is feasible in the clinical setting and requires only a minor increase in examination time.

Methamphetamine causes microglial activation in the brains of human abusers.

Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, and education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [(11)C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([(11)C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [(11)C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [(11)C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (>250% higher; p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence.

Striatal D2 receptor availability after shunting in idiopathic normal pressure hydrocephalus.

UNLABELLED: Gait disturbance in idiopathic normal pressure hydrocephalus (iNPH) is reminiscent of parkinsonism. Our recent PET study showed reduction in postsynaptic D(2) receptor binding concomitant with a normality of presynaptic dopamine transporter binding. Here, we investigated the plasticity of D(2) receptor in treating iNPH patients with ventriculoperitoneal (VP) shunting using PET with (11)C-raclopride and discuss the contribution of D(2) receptor to the pathophysiology of iNPH. METHODS: Eight iNPH patients participated in this study. After evaluation of their neuropsychologic abilities, all patients underwent 3-dimensional MRI and quantitative PET measurements twice before and 1 mo after VP shunting. MRI-based morphometric analyses were performed to examine postoperative variations of the ventricles. Estimation of binding potential (BP) for (11)C-raclopride was based on Logan plot analysis. Region-of-interest analysis was used to examine changes in (11)C-raclopride BP in the striatum. A 2-tailed paired t test was used for evaluating changes in PET and MRI parameters between conditions, and correlation analysis was used to investigate clinicopathophysiologic relevance (clinical vs. in vivo findings). RESULTS: Clinical evaluation revealed significant recovery in a 5-m back-and-forth navigation test and an affect test and a mild increase in Mini-Mental State Examination scores after VP shunting. Significant postoperative increases in (11)C-raclopride BP were found in the nucleus accumbens and dorsal putamen, and the increases were significantly associated with emotional (Spearman rank r = 0.66, P < 0.05) and navigational improvement (r = 0.72, P < 0.05), respectively. The (11)C-raclopride BP increase in the striaum as a whole correlated significantly with improvement in general cognitive ability. There was a mild ventricular shrinkage after surgery, albeit there was no correlation of its size with clinical and PET parameters. CONCLUSION: Striatal upregulation of D(2) receptor after VP shunting is associated with amelioration of hypokinetic gait disturbance and anhedonic mentation in iNPH patients, indicating that the effect of VP shunting may reside in noninhibition of functionally suppressed D(2) receptor in the striatum. D(2) receptor responsiveness may indicate a mechanism for iNPH pathophysiology.

[Measurement of radiation exposure to a PET institution driver from patients injected with FDG].

With the recent increase in FDG-PET examinations, concern has mounted regarding radiation exposure to hospital staff and the general public from patients injected with FDG. Because our PET institution is located 15 km from the hospital that provides these examinations, a driver has been designated to transport patients injected with FDG. This study was designed to measure the radiation dose to the driver from these patients (n=28) and to compare it with the estimated dose. A pocket dosimeter was used to measure radiation exposure to the driver. When the distances between the driver and patient were 1.1 m and 1.9 m, mean measured doses were 7.31 microSv and 2.26 microSv, respectively, while mean estimated doses were 8.61 microSv and 2.82 microSv, respectively, per trip. It was presumed that maximum radiation exposure per year was between 3.02 mSv (1.1 m) and 0.92 mSv (1.9 m). According to our data, the measured dose was 20% lower than the estimated dose. This discrepancy may be due to the difference between the volume source (measured dose) and point source (estimated dose).

FDG PET for the assessment of myometrial infiltration in clinical stage I uterine corpus cancer.

OBJECTIVE: For surgical planning of uterine corpus cancer, prior knowledge of the depth of myometrial invasion is important. Curative tumour resection is possible in superficial invasion (stages IA and IB), while post-surgical chemotherapy or radiation therapy is required in deep invasion (stage IC). We evaluated the value of positron emission tomography with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG PET) for estimating the myometrial invasion in uterine corpus cancer. METHODS: We studied 22 patients with clinical stage I uterine corpus cancer, who underwent FDG PET prior to surgery. Standardized uptake value (SUV; tracer activity per injected dose normalized to body weight) was calculated on the PET image. PET findings were compared with magnetic resonance imaging (MRI) and the surgical staging. RESULTS: The surgical stage was IA in five, IB in 11 and IC in six patients. SUVs in deep invasion (15.69+/-4.73, 8.83-21.84) were significantly higher than those in superficial invasion (9.09+/-3.29, 2.68-15.41) (P<0.005). Using 12.0 as a cut-off value of SUV for the differentiation of these two groups, PET results were correct in 19 patients but were incorrect in three patients. Although both PET and MRI provided correct staging in 14 patients, only MRI overestimated the myometrial invasion in four patients with stage IB and showed inconclusive findings in one patient with stage IC. Four of these five patients were post-menopausal. CONCLUSIONS: The cut-off value of SUV (=12.0) may be a useful index for the differentiation of superficial invasion and deep invasion. FDG PET may be feasible for predicting the myometrial infiltration of uterine corpus cancer, especially when uterine atrophy makes it difficult at MRI in post-menopausal patients.

Reduction of serotonin transporters of patients with chronic fatigue syndrome.

To assess the involvement of serotonin in the symptoms of chronic fatigue syndrome, we investigated the serotonergic neurotransmitter system of chronic fatigue syndrome patients by the positron emission tomography (PET). Here we show that the density of serotonin transporters (5-HTTs) in the brain, as determined by using a radiotracer, [C](+)McN5652, was significantly reduced in the rostral subdivision of the anterior cingulate as compared with that in normal volunteers. This subdivision is different from that in the dorsal anterior cingulate in which binding potential values of individual patient showed a weak negative correlation with self-reported pain score of the patients. Therefore, an alteration of serotonergic system in the rostral anterior cingulate plays a key role in pathophysiology of chronic fatigue syndrome.

Early therapy monitoring with FDG-PET in aggressive non-Hodgkin's lymphoma and Hodgkin's lymphoma.

This study was designed to determine the value of 2-[fluorine-18]-fluoro-2-deoxy- d-glucose positron emission tomography (FDG-PET) in the early assessment of therapy response in lymphoma patients. We studied 20 patients with pathologically proven lymphoma, including 17 patients with aggressive non-Hodgkin's lymphoma and three patients with Hodgkin's lymphoma. All patients underwent whole-body FDG-PET imaging at baseline and after 1-2 cycles of chemotherapy. PET images were analysed visually and quantitatively by calculating the standardised uptake value (SUV). In each patient, we measured the SUV of the tumour demonstrating the highest FDG uptake at baseline study and the SUV of the same tumour after 1-2 cycles of therapy. The achievement of complete response was assessed on the basis of a combination of clinical findings and the results of conventional imaging modalities. Follow-up of progression-free survival (PFS) was obtained for the validation of PET data. Of the 20 patients, ten achieved complete remission at the completion of chemotherapy and the other ten did not respond to chemotherapy. Of the ten responders, four are still in remission (PFS 24-34 months) while the other six have relapsed (PFS 8-16 months). For the prediction of 24-month clinical outcome, visual analysis of PET after 1-2 cycles showed high sensitivity (87.5%) and accuracy (80%) but low specificity (50%). Comparison with the baseline SUVs revealed that the responders showed a significantly greater percent reduction in SUV after 1-2 cycles of therapy as compared with the non-responders (81.2%+/-9.5% vs 35.0%+/-20.2%, P<0.001). In addition, using 60% reduction as a cut-off value, the responders were clearly separated from the non-responders, with the exception of one non-responder. In conclusion, when performed early during chemotherapy, FDG-PET may be predictive of clinical outcome and allows differentiation of responders from non-responders in cases of aggressive lymphoma.

Imaging of gynecologic tumors: comparison of (11)C-choline PET with (18)F-FDG PET.

UNLABELLED: This study was designed to compare the value of PET using (11)C-choline with that of PET using (18)F-FDG for the diagnosis of gynecologic tumors. METHODS: We examined 21 patients, including 18 patients with untreated primary tumors and 3 patients with suspected recurrence of ovarian cancer. (11)C-choline PET and (18)F-FDG PET were performed within 2 wk of each other on each patient. The patients fasted for at least 5 h before the PET examinations, and PET was performed 5 min ((11)C-choline) and 60 min ((18)F-FDG) after injection of each tracer. PET images were corrected for the transmission data, and the reconstructed images were visually analyzed. Then, the standardized uptake value (SUV) was calculated for quantitative assessment of tumor uptake. PET results were compared with surgical histology or >6 mo of clinical observations. RESULTS: Of 18 untreated patients, (11)C-choline PET correctly detected primary tumors in 16 patients, whereas (18)F-FDG PET detected them in 14 patients. In 1 patient with small uterine cervical cancer and 1 diabetic patient with uterine corpus cancer, only (11)C-choline PET was true-positive. Both tracers were false-negative for atypical hyperplasia of the endometrium in 1 patient and were false-positive for pelvic inflammatory disease in 1 patient. For the diagnosis of recurrent ovarian cancer (n = 3), (11)C-choline PET and (18)F-FDG PET were true-positive in 1 patient, whereas neither tracer could detect cystic recurrent tumor and microscopic peritoneal disease in the other 2 patients. In the 15 patients with true-positive results for both tracers, tumor SUVs were significantly higher for (18)F-FDG than for (11)C-choline (9.14 +/- 3.78 vs. 4.61 +/- 1.61, P < 0.0001). In 2 patients with uterine cervical cancer, parailiac lymph node metastases were clearly visible on (18)F-FDG PET but were obscured by physiologic bowel uptake on (11)C-choline PET. CONCLUSION: The use of (11)C-choline PET is feasible for imaging of gynecologic tumors. Unlike (18)F-FDG PET, interpretation of the primary tumor on (11)C-choline PET is not hampered by urinary radioactivity; however, variable background activity in the intestine may interfere with the interpretation.

Ovarian cancer recurrence: role of whole-body positron emission tomography using 2-[fluorine-18]-fluoro-2-deoxy- D-glucose.

This study was designed to assess the value of whole-body positron emission tomography (PET) using 2-[fluorine-18]-fluoro-2-deoxy- D-glucose (FDG) for the diagnosis of recurrent ovarian cancer. Twenty-five patients who had previously undergone surgery for ovarian cancer were imaged using whole-body FDG-PET. During the 4 weeks preceding the PET study, conventional imaging, comprising computed tomography (CT) and magnetic resonance (MR) imaging of the abdomen and/or pelvis, was performed and serum CA125 levels were measured. PET imaging was commenced at 60 min after the intravenous administration of FDG in all patients. PET results were compared with the results of conventional imaging and CA125 levels, and related to pathological findings and clinical follow-up for more than 6 months. FDG-PET showed a sensitivity of 80% (16/20), a specificity of 100% (5/5) and an accuracy of 84% accuracy (21/25) for the diagnosis of recurrent ovarian cancer. The sensitivity, specificity and accuracy of conventional imaging were 55% (11/20), 100% (5/5) and 64% (16/25), respectively. PET could detect recurrent lesions in seven of nine patients in whom conventional imaging was falsely normal, while conventional imaging was true positive in two of four patients with false-negative PET results. The CA125 results showed a sensitivity of 75% (15/20), a specificity of 100% (5/5) and an accuracy of 80% accuracy (20/25). Among the 15 patients with true-positive CA125 results, PET correctly detected abnormal foci of recurrence in 13 patients (86.7%) whereas conventional imaging showed recurrent lesions in only eight patients (53.3%). In conclusion, our preliminary study demonstrates that FDG-PET may be accurate and useful for the detection of tumour recurrence when conventional imaging is inconclusive or negative, especially in patients with abnormal CA125 levels.