Prognostic value of volumetric metabolic parameter changes determined by during and after radiotherapy-based 18 F-FDG PET/CT in stage III non-small cell lung cancer.

The aim of this prospective study was to evaluate the prognostic value of volumetric metabolic parameters assessed by during and after radiation-based therapy 18 F-FDG PET/CT in patients with stage III non-small cell lung cancer (NSCLC). We enrolled stage III NSCLC patients who had planned to receive definitive chemo-radiation or radiotherapy (RT) and underwent 18 F-FDG PET/CT before treatment (PET1), during RT (at the fifth week, PET2) and after treatment (3 months later, PET3). By comparing with PET1, percentage changes of metabolic tumor volume (ΔMTV) and tumor total lesion glycolysis (ΔTLG) of PET2 and PET3 were calculated. We used medians of ΔTLG and ΔMTV as cut-off values to stratify patients. Their prognostic values were evaluated by progression-free survival (PFS) and overall survival (OS). Thirty patients were enrolled initially. Five were excluded due to multiple metastases or double cancer. The remaining 25 patients had PET2 at a median of 46 Gy. Data on PET3 were available in 19 patients. During-RT ΔTLG (cut-off: 65%) was a significant prognostic factor for PFS (P = 0.02) and OS (P < 0.01). During-RT ΔMTV (cut-off: 42%) had marginal significance for PFS (P = 0.07) and was significant for OS (P = 0.02). Of the PET3 parameters, neither ΔTLG nor ΔMTV was a significant prognostic factor for PFS and OS. We conclude that ΔTLG of during-RT 18 F-FDG PET/CT may predict treatment response and thus provide opportunities to modify treatment for poor responders.

SH3BGRL3 Protein as a Potential Prognostic Biomarker for Urothelial Carcinoma: A Novel Binding Partner of Epidermal Growth Factor Receptor.

PURPOSE: Mass spectrometry-based biomarker discovery has clinical benefit. To identify novel biomarkers for urothelial carcinoma, we performed quantitative proteomics on pooled urine pairs from patients with and without urothelial carcinoma. EXPERIMENTAL DESIGN: Shot-gun proteomics using liquid chromatography-tandem mass spectrometry and stable isotope dimethyl labeling identified 219 candidate proteins. The potential implication of SH3 domain binding glutamic acid-rich protein like 3 (SH3BGRL3) was examined by immunoblotting of the urine (n = 13) and urothelial tumors (n = 32). Additional immunohistochemistry was performed on bladder cancer array (n = 1145) and correlated with tumor aggressiveness. Then, biologic functions and signaling pathways of SH3BGRL3 were explored using stable cell lines. RESULTS: The detectable urine SH3BGRL3 in patients with urothelial carcinoma was positively associated with higher histologic grading and muscle invasiveness of urothelial carcinoma. SH3BGRL3 is expressed in 13.9% (159/1145) of bladder cancer cohort and is positively associated with muscle invasion (P = 0.0028). SH3BGRL3 expression is associated with increased risk of progression in patients with nonmuscle-invasive bladder cancer (P = 0.032). SH3BGRL3 expression is significantly associated with a high level of epidermal growth factor receptor (EGFR) in bladder cancer (P < 0.0001). SH3BGRL3 promotes the epithelial-mesenchymal transition, cell migration, and proliferation of urothelial carcinoma in vitro. SH3BGRL3 interacts with phosphor-EGFR at Y1068, Y1086, and Y1173 through Grb2 by its proline-rich motif, and activates the Akt-associated signaling pathway. CONCLUSIONS: Evaluation of SH3BGRL3 expression status or urine content may identify a subset of patients with bladder cancer who may require more intensive treatment. SH3BGRL3 deserves further investigation as a cotargeting candidate for designing EGFR-based cancer therapies. Clin Cancer Res; 21(24); 5601-11. ©2015 AACR.

Differences of various region-of-interest methods for measuring dopamine transporter availability using 99mTc-TRODAT-1 SPECT.

This study was to investigate whether various region-of-interest (ROI) methods for measuring dopamine transporter (DAT) availabilities by single photon emission computed tomography (SPECT) are statistically different, whether results of medical research are thereby influenced, and causes of these differences. Eighty-four healthy adults with (99m)Tc-TRODAT-1 SPECT and magnetic resonance imaging (MRI) scans were included. Six major analysis approaches were compared: (1) ROI drawn on the coregistered MRI; (2) ROIs drawn on the SPECT images; (3) standard ROI templates; (4) threshold-ROIs; (5) atlas-based mappings with coregistered MRI; and (6) atlas-based mappings with SPECT images. Using the atlas-based approaches we assessed the influence of striatum ROIs by slice-wise and voxel-wise comparisons. In (5) and (6), three partial-volume correction (PVC) methods were also explored. The results showed that DAT availabilities obtained from different methods were closely related but quite different and leaded to significant differences in determining the declines of DAT availability per decade (range: 5.95-11.99%). Use of 3D whole-striatum or more transverse slices could avoid biases in measuring the striatal DAT declines per decade. Atlas-based methods with PVC may be the preferable methods for medical research.

The increment in standardized uptake value determined using dual-phase 18F-FDG PET is a promising prognostic factor in non-small-cell lung cancer.

PURPOSE: We aimed to determine whether the increment in the maximal standardized uptake value (SUVmax) of the primary lung tumour between the initial and delayed imaging by dual-phase (18)F-FDG PET has prognostic value in patients with non-small-cell lung cancer (NSCLC). METHODS: We reviewed the records of patients with NSCLC who underwent pretreatment dual-phase (18)F-FDG PET/CT scans acquired at 1 h and 2 h after injection. The SUVmax increment (SUVinc) of the primary lung tumour was the 2-h SUVmax minus the 1-h SUVmax. Univariate and multivariate analyses were used to assess the prognostic significance of SUVinc, retention index, whole-body total metabolic tumour volume, whole-body total lesion glycolysis (TLGwb), 1-h SUVmax, 2-h SUVmax, gender, age, performance status, histological subtype, T stage, N stage and clinical stage. RESULTS: The records of 187 consecutive patients were reviewed. The median follow-up time was 3.9 years. The estimated median progression-free survival (PFS) and overall survival (OS) were 1.3 years and 4.4 years, respectively. An SUVinc cut-off value of >1 had the best discriminative yield for PFS. The 3-year PFS and OS were 61.6 % and 87.8 % in patients with SUVinc ≤ 1 versus 21.1 % and 46.2 % in patients with SUVinc >1 (all P < 0.01). Using the forward stepwise multivariate Cox proportional hazards model, SUVinc, TLGwb, and clinical stage were significant factors for PFS (all P < 0.01). A subgroup analysis of 117 patients treated with surgery showed that SUVinc (P = 0.02) and clinical stage (P < 0.01) were significant prognostic factors for PFS. Furthermore, in stage I patients treated with surgery alone, SUVinc was the only significant prognostic factor (HR 28.07; 95 % CI 2.42 - 326.41). CONCLUSION: SUVinc determined from dual-phase (18)F-FDG PET is a promising prognostic factor for NSCLC. It adds to the value of dual-phase (18)F-FDG PET.

Value of case-based learning in a nuclear medicine clerkship.

PURPOSE: Medical imaging, including nuclear medicine, is a powerful tool for supporting learning in human morphology and physiology and understanding the nature of disease and response to treatment. The purposes of this study were to create a new case-based learning (CBL) model and to compare CBL and the traditional instructional approach (TIA) in a nuclear medicine clerkship. METHODS: Internal consistency and expert validity were assessed for the instrument. A quasi-experimental, two-group pretest-posttest design was used for this study. A combination of CBL and the TIA was applied to the experimental group and the TIA only to the control group. Subjects were 70 undergraduate year 5 medical students in a clerkship curriculum. Before and after the educational intervention, students were tested with the instrument. RESULTS: Cronbach's α coefficients of the instrument ranged from 0.79 to 0.95, indicating acceptable to strong internal consistency. For expert validity, the suitability and fitness of the instrument were verified. The overall score was significantly improved for the experimental group (from 3.51 to 3.65, P = .03) but not for the control group (from 3.48 to 3.44, P = .49). The experimental group also showed significantly improved scores in teacher assessment and learning satisfaction, the latter the only domain showing a significant difference of the differences (P = .020). CONCLUSIONS: The integration of CBL, allied with the TIA, into clinical clerkships provides medical students with the opportunity to learn a nuclear medicine curriculum in an interactive and case-based format tailored specifically for medical students.

Prognostic value of whole-body total lesion glycolysis at pretreatment FDG PET/CT in non-small cell lung cancer.

PURPOSE: To determine whether whole-body total lesion glycolysis (TLG), which combines volumetric and metabolic information from fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), can provide a better evaluation of the prognosis for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The institutional review board approved this retrospective study, and the requirement to obtain informed consent was waived. The authors identified 105 consecutive patients with NSCLC who underwent staging FDG PET/CT before any therapy. These patients were free of brain metastasis and underwent standard treatment and subsequent clinical follow-up. Metabolic tumor volume (MTV), mean standardized uptake value (SUV), and maximum SUV of each tumor over the whole body were determined. Whole-body MTV and whole-body TLG are the summation of all the MTVs and summation of individual tumor volume multiplied by its mean SUV, respectively. Univariate and multivariate analyses were performed to assess the prognostic significance of whole-body TLG and other factors, including whole-body MTV, lung TLG, lung MTV, maximum SUV, sex, age, performance status, histologic subtype, T stage, N stage, clinical stage, and treatment method. RESULTS: The median follow-up time was 3.1 years. The estimated median progression-free survival (PFS) and overall survival (OS) for the cohort was 10.8 months and 2.8 years, respectively. The 1-year PFS was 0.0% for patients with high whole-body TLG (>655) and 50.0% for those with low whole-body TLG (≤655). The 1-year OS was 58.8% for patients with high whole-body TLG and 84.1% for those with low whole-body TLG. Univariate analysis showed that whole-body TLG, whole-body MTV, lung TLG, lung MTV, maximum SUV, performance status, T stage, N stage, clinical stage, and treatment type (surgery vs other) were significant prognostic factors for PFS (P < .01 for all). With use of the forward stepwise multivariate Cox proportional hazards model, whole-body TLG (hazard ratio = 2.92; 95% confidence interval: 1.62, 5.26; P < .01) and surgical treatment (hazard ratio = 4.24; 95% confidence interval: 2.54, 7.07; P < .01) remained significant in PFS. CONCLUSION: Whole-body TLG is of prognostic value for NSCLC. It may be a promising tool for stratifying patients with NSCLC for risk-adapted therapies.

Tc-99m-HL91 imaging in the early detection of neuronal injury in a neonatal rat model of hypoxic ischemia.

OBJECTIVE: Hypoxic-ischemic insult in newborns results in progressive neuronal loss. For neuroprotective therapy to be effective, it is important to identify high-risk neonates soon after birth. 99mTc-labeled imaging agent, Tc-99m-HL91, developed as a putative hypoxic reagent, has been reported to demonstrate increased uptake in ischemic myocardium. We hypothesized that Tc-99m-HL91 is sensitive for the early identification of hypoxic-ischemic injury in neonatal rat brains. DESIGN: Laboratory investigation. SETTING: University research laboratory. SUBJECTS: Sprague-Dawley rat pups. INTERVENTIONS: Postnatal day-7 pups were divided into four groups: hypoxic-ischemia, hypoxia-only, ischemia-only, and controls. In the early (2 hrs), intermediate (20 hrs), and late (44 hrs) reoxygenation phases, Tc-99m-HL91 in vivo and ex vivo imaging and quantitative autoradiography were performed. Regions of interest were drawn to calculate the contrast ratio of Tc-99m-HL91 uptake between the ipsilateral and contralateral hemispheres. Pathology, cerebral blood flow, and blood-brain barrier damage were determined. MEASUREMENTS AND MAIN RESULTS: After hypoxic-ischemia, there were very few pyknotic neurons in the early phase, many pyknotic neurons in the intermediate phase, and extensive neuronal loss in the late phase postreoxygenation. Blood-brain barrier damage occurred in the early phase, progressed in the intermediate phase, and became extensive in the late phase. The hypoxia-only and ischemia-only pups showed no neuronal or blood-brain barrier damage and had higher cerebral blood flow postreoxygenation compared with the hypoxia-ischemia pups. Regions of interest analysis of in vivo and ex vivo images and autoradiography revealed significantly higher Tc-99m-HL91 contrast ratio at early and intermediate phases, not late phase of hypoxic-ischemic group. Hypoxic-ischemia group had significantly higher contrast ratio values in the early and intermediate phases than the hypoxia-only and ischemia-only groups. A contrast ratio value of 0.15 in the early phase on postnatal day 7 had a sensitivity of 0.95 and specificity of 0.89 in detecting significant hypoxic-ischemic lesions on postnatal day 21. CONCLUSION: Tc-99m-HL91 uptake is sensitive for the early detection of hypoxic-ischemic injury in neonatal brains.

Review analysis of the association between the prevalence of activated brown adipose tissue and outdoor temperature.

Brown adipose tissue (BAT) is important for regulating body weight. Environmental temperature influences BAT activation. Activated BAT is identifiable using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). (18)F-FDG PET/CT scans done between June 2005 and May 2009 in our institution in tropical southern Taiwan and BAT studies from PubMed (2002-2011) were reviewed, and the average outdoor temperatures during the study periods were obtained. A simple linear regression was used to analyze the association between the prevalence of activated BAT (P) and the average outdoor temperature (T). The review analysis for 9 BAT studies (n = 16, 765) showed a significant negative correlation (r = -0.741, P = 0.022) between the prevalence of activated BAT and the average outdoor temperature. The equation of the regression line is P(%) = 6.99 - 0.20 × T (°C). The prevalence of activated BAT decreased by 1% for each 5°C increase in average outdoor temperature. In a neutral ambient temperature, the prevalence of activated BAT is low and especially rare in the tropics. There is a significant linear negative correlation between the prevalence of activated BAT and the average outdoor temperature.

The relationship between brown adipose tissue activity and neoplastic status: an (18)F-FDG PET/CT study in the tropics.

BACKGROUND: Brown adipose tissue (BAT) has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[(18)F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in people living in the tropics, where the influence of outdoor temperature was low. METHODS: (18)F-FDG PET/CT scans were reviewed and the total metabolic activity (TMA) of identified activated BAT quantified. The distribution and TMA of activated BAT were compared between patients with and without a cancer history. The neoplastic status of patients was scored according to their cancer history and (18)F-FDG PET/CT findings. We evaluated the relationships between the TMA of BAT and neoplastic status along with other factors: age, body mass index, fasting blood sugar, gender, and outdoor temperature. RESULTS: Thirty of 1740 patients had activated BAT. Those with a cancer history had wider BAT distribution (p = 0.043) and a higher TMA (p = 0.028) than those without. A higher neoplastic status score was associated with a higher average TMA. Multivariate analyses showed that neoplastic status was the only factor significantly associated with the TMA of activated BAT (p = 0.016). CONCLUSIONS: Neoplastic status is a critical determinant of BAT activity in patients living in the tropics. More active neoplastic status was associated with more vigorous TMA of BAT.

Relationship between striatal dopamine transporter availability and sleep quality in healthy adults.

PURPOSE: Our previous study using (123)I-iodo-benzamide single photon emission computed tomography (SPECT) showed a positive relationship in healthy adults between striatal postsynaptic D(2)/D(3) receptor availability and sleep duration in good sleepers. To further investigate the role of dopamine (DA) in the sleep-wake cycle, we explored the correlation between presynaptic dopamine transporter (DAT) availability and sleep quality in healthy volunteers. METHODS: A total of 83 healthy volunteers (33 males, 50 females; mean age, 34.62 years), including 39 good sleepers and 44 poor sleepers, were recruited. The sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Striatal DAT availability was determined by (99m)Tc-TRODAT-1 SPECT, and the DAT availability in the good and poor sleepers was compared. Furthermore, the correlation between PSQI and DAT availability was analyzed. RESULTS: There was no significant difference in DAT availability between the good and poor sleepers. No significant relationship was found between the global score or individual-component PSQI scores and DAT availability in the good sleepers. However, the sleep duration component score in the poor sleepers negatively correlated with DAT availability in the caudate (ρ = -0.31, P = 0.049). CONCLUSIONS: The study demonstrates that healthy poor sleepers, with a lower DAT availability in the caudate, sleep for a shorter length of time. This suggests that a decrease in DA reuptake due to reduced DAT availability causes a shorter sleep duration in poor sleepers.

Angiographic-CT-FDG-Pathologic Correlations of the Incidentally Discovered Adrenal Mass.

During abdominal ultrasonography of a 37-year-old man a 3.2 cm hypoechoic mass in the right hepatic lobe was found incidentally. This prompted an abdominal CT, an FDG PET/CT, and an angiography to evaluate the nature of the mass. Laboratory data showed positive anti-HBs/anti-HBe, and negative HCV antibody. The alfa-fetoprotein and liver function tests were within normal limits. Contrast-enhanced CT found an enhanced hepatic tumor and primary hepatocellular carcinoma was suspected. PET/CT revealed no abnormal FDG accumulation in the right hepatic mass. The digital subtraction angiographies of the right inferior phrenic artery and right renal artery revealed a hypervascular tumor in the right adrenal gland. Therefore, a diagnosis of a right adrenal tumor was made. Serum aldosterone, serum cortisol, and urine vanillylmandelic acid, and catecholamine were all within normal limits. Laparoscopic right adrenalectomy was performed and adrenal cortical adenoma was diagnosed on a histological study.

A false positive F-FDG PET/CT scan caused by breast silicone injection.

We present here the case of a 40-year-old woman with a greater than 10 year prior history of bilateral breast silicone injection and saline bag implantation. Bilateral palpable breast nodules were observed, but the ultrasound scan was suboptimal and the magnetic resonance imaging showed no gadolinium-enhanced tumor. The (18)F-FDG PET/CT scan showed a hypermetabolic nodule in the left breast with a 30% increase of (18)F-FDG uptake on the delayed imaging, and this mimicked breast cancer. She underwent a left partial mastectomy and the pathology demonstrated a siliconoma.

Accumulation of Tc-99m HL91 in tumor hypoxia: in vitro cell culture and in vivo tumor model.

Hypoxic cells within a tumor can account, in part, for resistance to radiotherapy and chemotherapy. Indeed, the oxygenation status has been shown to be a prognostic marker for the outcome of therapy. The purpose of this study was to determine whether Tc-99m HL91 (HL91), a noninvasive imaging tracer, detects tumor hypoxia in vitro in cell culture and in vivo in a tumor model. Uptake of HL91 in vitro into human lung cancer cells (A549) and murine Lewis lung cancer cells (LL2) was investigated at oxygen concentrations of 20% O2 (normoxia), and 1% O2 (hypoxia). HL91 biodistribution was studied in four groups: severe combined immune deficiency (SCID) mice bearing A549 tumors, C57BL/6NCrj (B6) mice bearing LL2 tumors, SCID controls, and B6 controls. Accumulation of the tracer was compared between tumors treated with hydralazine or phosphate-buffered saline (PBS). Scintigraphic images were obtained for hydralazine-treated mice and PBS-treated mice in each of the four study groups. Autoradiography of tumor slices was also acquired. In vitro studies identified hypoxia-selective uptake of HL91, with significantly increased uptake in the hypoxic state than in the normoxic state. Biodistribution and scintigraphy showed increased HL91 uptake during tumor hypoxia at 0.5 hours, and there was progressively increased activity for up to 4 hours after tracer administration. HL91 accumulation in tumor hypoxia was markedly increased in mice treated with hydralazine compared with those treated with PBS. Autoradiography revealed high HL91 uptake in the peripheral areas around the necrotic regions of the tumor, which were identified by histologic examination. HL91 exhibits selectivity for tumor hypoxia both in vitro and in vivo and provides a successful imaging modality for the detection of tumor hypoxia in vivo.

Peritoneal tuberculosis with elevated serum CA125 mimicking peritoneal carcinomatosis on F-18 FDG-PET/CT.

18F-fluorodeoxyglucose positron emission tomography (F-18 FDG-PET) plays an important role in differentiating benign from malignant tumors. However, some false-positive findings, such as tuberculosis, may occur. We report a case referred for F-18 FDG whole-body PET computed tomography (PET/CT) scan owing to an elevated serum cancer antigen 125 (CA125). An FDG-PET/CT scan showed multiple hypermetabolic foci in the mesentery and peritoneum with further increase of FDG uptake on the delayed scan, mimicking peritoneal carcinomatosis. Subsequent laparoscopic biopsy showed granulomatous inflammation, and tuberculosis polymerase chain reaction showed a positive result. Serum CA125 returned to normal following treatment with anti-tuberculosis drugs. Peritoneal tuberculosis should be considered as a differential diagnosis in a tuberculosis endemic region.

Dual-phase 18F-FDG PET in the diagnosis of pulmonary nodules with an initial standard uptake value less than 2.5.

OBJECTIVE: A cutoff standard uptake value (SUV) of 2.5 has been commonly adopted for (18)F-FDG PET to evaluate pulmonary lesions, but false results can occur. Studies have shown the usefulness of delayed PET for improving accuracy. This study was designed to examine the efficiency of delayed PET of pulmonary nodules with an initial mean SUV less than 2.5. MATERIALS AND METHODS: Dual-phase FDG PET studies were conducted with imaging 1 and 2 hours after FDG injection, and pulmonary lesions with an initial mean SUV less than 2.5 were identified. Nodules with pathologic reports were included in the study. The differences in mean SUV, maximal SUV, and retention index between benign and malignant pulmonary lesions were analyzed. Receiver operating characteristic analysis was performed to evaluate the discriminating validity of the retention index. RESULTS: A total of 31 lesions (15 benign, 16 malignant) were included in the study. Among the benign lesions, 12 were granulomatous inflammation, including 10 tuberculosis lesions and two cryptococcosis lesions, and three were focal fibrosis. A retention index greater than 0% was observed in 87% of the benign lesions; 60% of the benign lesions had a retention index greater than 10%. Among the malignant lesions, 75% had a retention index greater than 0%, and 62% had a retention index greater than 10%. We found no significant differences in mean SUV, maximal SUV, and retention index between benign and malignant lesions. The area under the receiver operating characteristic curve did not differ from 0.5. CONCLUSION: Delayed FDG PET is not useful for differentiating benign and malignant pulmonary nodules with an initial mean SUV less than 2.5 in geographic regions with epidemic granulomatous disease such as tuberculosis or in patients at high risk of granulomatous inflammation.

Evaluation of Tc-99m (V) DMSA binding to human plasma proteins.

As a critical step toward elucidating the mechanism of localization of Tc-99m (V) dimercaptosuccinic acid (DMSA), we investigated its binding and transport in blood in comparison with Ga-67 citrate. The studies were performed in vitro by incubating Tc-99m (V) DMSA with blood (one sample at 4 degrees Celcius and another at 37 degrees Celcius) to assess its binding to plasma proteins using ultrafiltration, dialysis, electrophoresis, gel filtration chromatography and affinity chromatography. A parallel experiment for determining the blood binding of Ga-67 citrate was performed using the same procedures. Using ultrafiltration, dialysis, electrophoresis and gel filtration chromatography, labeled plasma samples showed that protein binding for Tc-99m (V) DMSA was 45-54% at 37 degrees Celcius and 73-80% at 4 degrees Celcius. The figures for Ga-67 citrate were 43-53% at 37 degrees Celcius and 75-81% at 4 degrees Celcius. Electrophoresis showed that Tc-99m (V) DMSA was mostly bound to plasma albumin (36.05 +/- 2.48% at 37 degrees Celcius and 60.04 +/- 1.87% at 4 degrees Celcius), and that the proportion of Ga-67 radioactivity associated with beta-globulin was 34.23 +/- 1.37% at 37 degrees Celcius and 55.71 +/- 3.69% at 4 degrees Celcius. In affinity chromatography experiments, Tc-99m (V) DMSA did not bind to transferrin, unlike Ga-67 citrate. This study demonstrates that, at the radiopharmaceutical tracer level, most Tc-99m (V) DMSA in blood is protein-bound, primarily to albumin, but not to transferrin. In contrast, Ga-67 citrate was bound primarily to transferrin. The knowledge that albumin is the main transport protein of Tc-99m (V) DMSA may contribute to a better understanding of its biodistribution and pharmacokinetics.

The relation between striatal dopamine D2/D3 receptor availability and sleep quality in healthy adults.

PURPOSE: Increasing evidence, primarily from animal studies and patients with compromised neurotransmitter systems, indicates a possibly important role for dopamine in modulating sleep. We therefore conducted this study to explore the relation between sleep and dopamine in healthy adults. METHODS: We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Higher PSQI scores indicate a lower quality of sleep. Striatal dopamine D2/D3 receptor availability was determined using [123I]iodo-benzamide (IBZM) SPECT. Fifty-five healthy volunteers (32 men, 23 women; mean age, 36.7+/-12.1 years), including 25 good sleepers and 30 poor sleepers, were recruited. We analysed the correlation between the PSQI and D2/D3 receptor availability in good and poor sleepers based on Pearson's product-moment after removing the effects of gender and age. We also analysed differences in D2/D3 receptor availability between good and poor sleepers. RESULTS: In poor sleepers, there was no statistically significant relationship between the global, individual components of the PSQI score and D2/D3 receptor availability. However, in good sleepers, the score of the sleep duration component was significantly negatively correlated with D2/D3 receptor availability in the caudate. There was no significant difference in D2/D3 receptor availability between good and poor sleepers. CONCLUSION: Our findings demonstrate that healthy good sleepers with higher D2/D3 receptor availability in the caudate sleep longer. Poor sleep in healthy subjects might be not primarily related to the dopaminergic system.

Renal scarring sequelae in childhood Kawasaki disease.

To assess renal inflammation and its sequelae in Kawasaki disease (KD) patients, we conducted a prospective study in a university medical center setting in Taiwan. From June 2002 to January 2005, 50 children with KD were enrolled, and after admission, all received technetium-99m dimercaptosuccinic acid scintigraphy single photon emission computed tomography (DMSA renal SPECT), the results of which were used as the reference standard for determining renal inflammation. Patients with renal inflammation underwent another DMSA renal SPECT more than 6 months later to evaluate the sequelae. We found that 26 of the 50 patients (52%) had renal inflammatory foci. There were no significant relationships between clinical or laboratory parameters and renal involvement in KD, except the presence of coronary artery lesions [P<0.01; odds ratio (OR) 5.18; 95% confidence interval (CI) 1.52-17.65]. Although all patients were free of clinical symptoms, the 6-month follow-up DMSA renal SPECT showed renal scarring in 11 of the 24 patients (46%). Patients with an initial abnormal renal ultrasound did predict a greatly increased risk of scarring (P<0.05; OR 16.2; 95% CI 1.27-206.20). In conclusion, this study demonstrated that the potential long-term clinical impact of KD is not limited to coronary artery lesion sequelae but also includes renal scar formation.

Educational level influences regional cerebral blood flow in patients with Alzheimer's disease.

UNLABELLED: We tested the hypothesis that educational level influences regional cerebral blood flow (rCBF) in Alzheimer's disease (AD) patients. METHODS: The severity of AD was measured with the Cognitive Ability Screening Instrument (age and education adjusted). rCBF was assessed using (99m)Tc-hexamethylpropyleneamine oxime brain SPECT; differences in rCBF between groups with different educational levels were determined using statistical parametric mapping (SPM). RESULTS: In matched low-education (< or =6 y; n = 29) and high-education (>6 y; n = 29) groups, SPM revealed 2 statistically significant clusters of voxels with higher rCBF in the high-education group: one in the left lateral inferior, middle, and superior temporal gyrus; another in the left medial temporal area to the left inferior frontal gyrus. CONCLUSION: We provide biologic evidence that education may lead to relatively higher rCBF in specific areas in AD patients, which may explain the effects of education on clinical manifestations of AD.