Imaging of cardiac sympathetic dysfunction with 18F-FDOPA PET/CT in patients with heart failure: a pilot study.

BACKGROUND: Routine use of cardiac sympathetic imaging in HF has been limited by the lower availability/sensitivity of radiotracers. This study was aimed to assess the feasibility of 18F-FDOPA (commonly available PET-radiotracer) in assessment of cardiac autonomic dysfunction. METHODS: Twenty-four controls (46.5 ± 11.1 years, 16men) and 24 patients (43.5 ± 11.0 years, 18men) with diagnosed HF (Framingham-Criteria) underwent cardiac-PET/CT. Region(s) Of Interest were drawn over entire left ventricular myocardium (LV), individual walls, and mediastinum (M). Coefficient of Variation (CV) was calculated from individual wall counts. RESULTS: HF patients had significantly lower myocardial 18F-FDOPA uptake (P < .001, independent t test) than controls [32.4% ± 9.5% global reduction; highest in apex (39.9% ± 7.0%)]. A cut-off of LV/M ≤ 1.68 could differentiate patients from controls with sensitivity and specificity of 100% and 95.8%, respectively. LV/M correlated positively with EF (Pearson coefficient = 0.460, P .031). During follow-up, 3 patients were lost to follow-up, 4 died (survival-20.5 ± 4 months), 2 worsened, and 15 remained stable/showed mild improvement. Patients who worsened/died during follow-up had higher CV than those with stable/improving symptoms [0.16 ± 0.05 vs 0.11 ± 0.05, P value .069 (independent t test); Cox regression P = .084]. CONCLUSION: Myocardial 18F-FDOPA uptake in patients with HF is significantly reduced. Higher reduction is seen in those with lower EF. CV, a maker of regional heterogeneity, is a potential prognostic marker.

Assessment of myocardial sympathetic innervation with 18F-FDOPA-PET/CT in patients with autonomic dysfunction: feasibility study in IPD patients.

BACKGROUND: Dysfunction and denervation of myocardial nor-adrenergic sympathetic neurons has been documented in IPD patients with dysautonomia. The aim of this study was to evaluate the feasibility of single tracer imaging of myocardial sympathetic and cerebral striatal involvement in these patients. METHODS: Twenty-two controls (mean-age 59.09 ± 12.39 years, 15 men) with no clinical autonomic-dysfunction and normal striatal-uptake in 18F-FDOPA-PET/CT; and 28 patients (mean-age 58.18 ± 8.25 years, 18 men) with autonomic-dysfunction (in Autonomic Function Tests) and striatal dopaminergic-dysfunction were enrolled. Both cardiac-PET/CT (40 minutes post IV-injection of 185-259MBq 18F-FDOPA) and Brain-PET/CT (60 minutes post-IV) were acquired in same session. ROIs were drawn over the entire left ventricular myocardium, individual walls and mediastinum for quantification. Patients and controls were followed-up for 26.93 ± 5.43 months and 37.91 ± 8.63 months, respectively. RESULTS: Striatal and myocardial-parameters were significantly lower in patients compared to controls; with Myocardium/mediastinal ratio (MwMR) yielding the area-under-the-curve of .941 (P < .001). MwMR correlated negatively with the drop in systolic blood pressure (SBP) during AFTs {Pearson-coefficient (-).565, P = .002}. Mean MwMR in patients with abnormal-AFTs was significantly lower than patients with borderline-AFTs (1.39 ± .12 vs 1.55 ± .10; P = .002). 9/20 patients with abnormal-AFTs showed functional worsening during follow-up, compared to 2/8 with borderline-AFTs. CONCLUSION: Single tracer, single session imaging of striatal and cardiac sympathetic dysfunction in patients with advanced IPD is feasible with use of 18F-FDOPA. Significantly reduced 18F-FDOPA uptake is seen in the myocardium of the IPD patients with sympathetic dysfunction.

Dopamine transporter availability in alcohol and opioid dependent subjects - a 99mTc-TRODAT-1SPECT imaging and genetic association study.

Drug dependence associated with increased dopamine neurotransmission and neuroplastic changes is influenced by Dopamine transporters (DAT) which are modulated by genetic and epigenetic factors. This study assesses DAT availability in relation to the 40bp DAT1 VNTR (genetic) and DAT1 promoter methylation (epigenetic) changes in patients with alcohol dependence (AD) and opioid dependence (OD). A total of 60 subjects (n=20 each of AD, OD and controls) were recruited. SPECT/CT imaging using 99mTc-TRODAT-1 was performed for measuring striatal DAT availability and DNA screened to check DAT1promoter methylation and 40bp VNTR polymorphism. SPECT/CT imaging revealed significant decrease in DAT availability in the striatum and putamen and significant increase in DAT1 promoter methylation in AD compared to control and OD. The 40bp VNTR distribution was similar in all three groups with 10repeat and 9repeat alleles being the most common. The AD individuals with DAT1promoter methylation showed significantly lower TRODAT-1 uptake compared to the ones with no methylation. AD individuals homozygous for the 10repeat VNTR also showed reduced DAT availability. This is the first imaging study using 99mTc-TRODAT-1 from India documenting significantly reduced striatal DAT availability, increased DAT methylation and frequency of 10repeat individuals associated with decreased DAT availability in AD.

Serum FOXO3A: A ray of hope for early diagnosis of Alzheimer's disease.

Diagnosis of Alzheimer's disease (AD) is often difficult because of distinct and subjective clinical features, especially in the early stage. FOXO3a protein present in the cognitive centre of brain in inferior temporal region and parahippocampus. FOXO3a can be a potential novel target against AD. AD, Mild Cognitive impairment (MCI) and Geriatric Control (GC) were recruited after diagnosis by clinical assessment, MRI, TauPET and FDG-PET. We have quantified serum FOXO3a by surface plasmon resonance (SPR) and compare with TauPET between of AD, MCI patients and GC. Serum FOXO3A was significantly lower in AD (1.42 ± 0.09 ng/µl) compare to MCI (1.61 ± 0.14 ng/µl) and GC (1.89 ± 0.07 ng/µl). However, the Tau was higher in AD both in serum and also in PET scan. Serum pTau was significantly over-expressed in AD (0.176 ± 0.03 ng/µl), compare to other groups; MCI (0.16 ± 0.014 ng/µl) and GC (0.15 ± 0.024 ng/µl). Serum FOXO3A could significantly differentiate AD vs MCI, MCI vs GC and AD vs GC. However, Tau protein could only differentiate AD vs GC but not MCI vs GC. Serum FOXO3A may serve as novel blood marker for early detection for AD and target for therapeutic intervention.

Neuroendocrine tumour of urinary bladder: a rare case of aggressively behaving primary well-differentiated neuroendocrine tumour with review of literature.

Neuroendocrine tumour (NET) of the urinary bladder (UB) is a rare entity and comprises of well-differentiated, small cell and large cell types. Small and large cell NET like that in lung and gastrointestinal tract have an aggressive nature and are considered high-grade disease. Well-differentiated NET has been thought to be localised and having a good prognosis. We report the first case of metastatic well-differentiated NET of the UB. Our case is a 44-year-old man with well-differentiated NET of UB presented with hepatic and peritoneal metastases on initial diagnosis. He was treated with metaiodobenzylguanidine (MIBG) therapy and had a modest survival of 16 months. The primary well-differentiated NETs can present as a metastatic disease with an aggressive nature. MIBG therapy can be considered as a useful option but overall prognosis is poor. Further research is needed for better understanding and better treatment protocol.

Brain Plasticity and Neurophysiological Correlates of Meditation in Long-Term Meditators: A 18Fluorodeoxyglucose Positron Emission Tomography Study Based on an Innovative Methodology.

Objective: Previous studies evaluating neurophysiological correlates of long-term meditation are constrained by some methodological limitations. The objective of this study was to measure changes in the regional cerebral glucose metabolism during meditation using a novel methodological approach. Design: The present study was a part of a larger, nonrandomized, single-center open-label study. Setting/location: The study was conducted at the Department of Physiology and Department of Nuclear Medicine and Positron Emission Tomography. A dedicated place was set up as a yoga room, away from the positron emission tomography (PET) scanning room in the Department of Nuclear Medicine and Positron Emission Tomography, where meditators performed meditation in a peaceful environment in a sitting posture with eyes closed. The electroencephalography (EEG) was recorded to affirm the meditation objectively. Subjects: Twenty-four sets of PET scans were obtained at 2 different occasions (baseline and postmeditation within 40 min of 18FDG [18fluorodeoxyglucose] injection) from 12 apparently healthy, male, right-handed long-term meditators practicing Preksha meditation (since >5 years, at least 5 days a week) who were recruited from a well-established meditation center in Delhi. Outcome measures: Changes in the regional cerebral glucose metabolism during meditation versus baseline. Results: Regional cluster analysis showed significantly activated well-defined areas of fronto-parieto-temporal regions of the right versus left hemisphere during meditation. Interestingly, right homolog of Broca's area and right lentiform nucleus were hyperactive during meditation in all the meditators. Conclusions: Long-term meditation might potentially enhance the explicit functions of specific parts of the right hemisphere, possibly due to neuroplastic changes in the brain. Importantly, results of the current study are encouraging and show a novel methodological approach to acquire 18FDG PET/CT (computed tomography) images. The study was registered at Clinical Trial Registry India (CTRI), CTRI/2009/091/000727.

Effect of basal ganglia calcification on its glucose metabolism and dopaminergic function in idiopathic hypoparathyroidism.

BACKGROUND: The functional significance of basal ganglia calcification (BGC) in idiopathic hypoparathyroidism (IH) is not clear. OBJECTIVE: To assess the effect of BGC on glucose metabolism and dopaminergic function in IH. METHODS: (18) F-FDG and (99m) Tc-TRODAT-1 nuclear imaging were performed in 35 IH patients with (n = 26) and without (n = 9) BGC. Controls were subjects without hypoparathyroidism or BGC (nine for (18) F-FDG and 12 for (99m) Tc-TRODAT-1). Relationship of the glucose metabolism and dopaminergic function was assessed with the neuropsychological and biochemical abnormalities. RESULTS: (18) F-FDG uptake in IH patients with calcification at caudate and striatum was less than that of IH patients without calcification (1·06 ± 0·13 vs 1·24 ± 0·09, P = <0·0001 and 1·06 ± 0·09 vs 1·14 ± 0·08, P = 0·03, respectively). (18) F-FDG uptake did not correlate with neuropsychological dysfunctions. (18) F-FDG uptake in IH without BGC was significantly lower than that of controls. The mean (99m) Tc-TRODAT-1 uptake at basal ganglia was comparable between IH with and without BGC and between IH without BGC and controls. Serum calcium-phosphorus ratio maintained by the patients correlated with (18) F-FDG uptake at striatum (r = 0·57, P = 0·001). For every 0·1 unit reduction in calcium-phosphorus ratio, (18) F-FDG uptake decreased by 2·5 ± 0·68% (P = 0·001). CONCLUSION: BGC was associated with modest reduction (15%) in (18) F-FDG uptake at basal ganglia in IH but did not affect dopaminergic function. (18) F-FDG uptake did not correlate with neuropsychological dysfunctions. Interestingly, chronic hypocalcaemia-hyperphosphataemia also contributed to reduction in (18) F-FDG uptake which was independent of BGC.

Pulmonary alveolar microlithiasis: imaging characteristics of planar and SPECT/CT bone scan versus 18F-FDG and 18F-sodium fluoride PET/CT scanning.

Pulmonary alveolar microlithiasis (PAM) is a very rare disease in which multiple microscopic calcium phosphate microliths are deposited within the alveoli of both lungs. A lung biopsy is considered to be definitive for final diagnosis; however, non-invasive imaging modalities such as chest X-ray, HRCT scan and (99m)Tc-MDP bone scan suggest the diagnosis in the vast majority of patients. Although (18)F-FDG PET/CT has been tried to characterize the disease, (18)F-sodium fluoride PET/CT as a 'proof-of-principle' was tried for the first time in a known case of PAM in order to characterize the lung lesions. Interestingly, we noted that (18)F-sodium fluoride PET/CT is a superior modality in characterization and assessment of the extent of disease in PAM compared to all other non-invasive imaging modalities. Thus, we recommend that (18)F-sodium fluoride PET/CT should be the investigation of choice in PAM.

Effect of enalapril on glomerular filtration rate and proteinuria in children with chronic kidney disease: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of enalapril treatment on decline in glomerular filtration rate and reduction in proteinuria in children with chronic kidney disease (CKD). DESIGN: Open-label, randomized controlled trial. SETTING: Pediatric nephrology clinic at a tertiary-care referral hospital. INTERVENTION: Children with GFR between 15-60 mL/min/1.73 m2 were randomized to receive either enalapril at 0.4 mg/kg /day or no enalapril for 1 year. OUTCOME MEASURES: Change in GFR using 99mTc-DTPA and urine protein to creatinine ratio. Secondary outcomes included occurrence of composite outcome (30% decline in GFR or end stage renal disease) and systolic and diastolic blood pressure SDS during the study period. RESULTS: 41 children were randomized into two groups; 20 received enalapril while 21 did not receive enalapril. During 1 year, GFR decline was not different in the two groups (regression coefficient (r) 0.40, 95% CI -4.29 to 5.09, P=0.86). The mean proteinuria reduction was 65% in the enalapril group, significantly higher than control group. The difference was significant even after adjustment for blood pressure was 198.5 (CI 97.5, 299.3; P<0.001). 3 (17.6%) patients in enalapril and 7 (36.8%) in non-enalapril group attained the composite outcome. CONCLUSIONS: Enalapril is effective in reducing proteinuria in children with CKD and might be renoprotective in proteinuric CKD.

FDG PET/CT evaluation of treatment response in patients with recurrent colorectal cancer.

AIM: to evaluate the treatment response in patients with recurrent colorectal cancer (CRC) using FDG PET/CT. MATERIALS AND METHODS: a total of 32 recurrent CRC patients (21 males, 11 females; mean age, 52.8 years) were included in this retrospective study. All patients underwent a baseline and follow-up FDG PET/CT scans after chemotherapy. Of 32 patients, 23 patients had follow-up carcinoembryonic antigen (CEA) levels. RESULTS: on qualitative analysis of baseline and follow-up FDG PET/CT studies, there were 20 nonresponders and 12 were responders. On quantitative analysis, there were 19 nonresponders and 13 were responders. In responders, baseline and follow-up mean SUV(max) were 11.8 ± 10.1 and 3.7 ± 4.1, respectively (significant decrease, P = 0.001). Among nonresponders, baseline and follow-up mean SUV(max) were 8.1 ± 5.2 and 14.1 ± 9.0, respectively (significant increase, P = 0.003). There was no association between response and different factors like age, sex, diagnosis, extent of the lesions, and number of lesions. CONCLUSION: FDG PET/CT appears to be useful modality in evaluating chemotherapy response and can differentiate responders from nonresponders in recurrent CRC patients.

Role of FDG-PET/CT in detection of recurrent disease in colorectal cancer.

BACKGROUND: One-third of patients with colorectal cancer (CRC) are likely to have a recurrence within the first 1-2 years. Conventional imaging modalities have limitations in detecting recurrent disease early. The purpose of this study was to assess the usefulness of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in the detection of recurrence in patients with CRCs. METHODS: One hundred and eighty-three patients, who were earlier treated with surgery and/or chemotherapy/radiotherapy, underwent 269 PET/CT studies for the detection of recurrence. The final diagnosis was made on the basis of histological analysis or clinical and imaging follow-up. RESULTS: The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value in detecting recurrent CRC using F-FDG-PET/CT were 87, 90, 88, 93, and 80%, respectively. PET/CT was found to have limitations in detecting microscopic disease and small-sized lesions. The common cause of false-positive PET/CT results was infective and inflammatory pathology in our setup. CONCLUSION: PET/CT showed high sensitivity, specificity, and accuracy for the detection of recurrent disease in patients, who were earlier treated for CRC. PET/CT can be considered as a useful diagnostic tool in these patients.

Bilateral primary renal lymphoma with orbital metastasis in a child.

Primary renal lymphoma (PRL) is a rare condition and bilateral PRL even rarer. Most of these bilateral PRL have been reported in adults. We describe a 3-year-old male with bilateral primary renal B cell lymphoma with orbital metastases. We discuss the difficulties in diagnosis and management of this rare presentation of lymphoma.

A female with hemihypertrophy and chylous ascites - Klippel-Trenaunay syndrome or Proteus syndrome: a diagnostic dilemma.

Asymmetric overgrowth has many differential diagnoses with considerable overlap, posing a diagnostic dilemma. The presence of chylous ascites, though unreported, might be expected as a manifestation of overgrowth syndromes with lymphatic involvement. We present a patient with hemihypertrophy who presented with chylous ascites at birth.

Randomized, double-blind, placebo-controlled trial to evaluate efficacy of ketodiet in predialytic chronic renal failure.

OBJECTIVE: To assess whether a ketodiet, a combination of ketoanalogs of essential amino acids (KAs) and a very low-protein diet, retards progression of chronic renal failure and maintains nutritional status. DESIGN: A prospective, randomized, double-blind, placebo-controlled trial. SETTING: Nephrology outpatient department in Northern Railways Central Hospital, New Delhi, India. PATIENTS: Thirty-four patients in predialytic stages of chronic renal failure (CRF), randomized to 2 comparable groups in terms of age, sex distribution, blood pressure control, etiology, use of angiotensin converting enzyme inhibitors, serum creatinine, glomerular filtration rate (GFR), and body mass index (BMI). INTERVENTION: Subjects randomly received either 0.6 g/kg/d protein plus placebo (n = 16) or 0.3 g/kg/d protein plus tablets of KAs (Ketosteril; Fresenius Kabi, Germany) (n = 18) for 9 months. A dietician administered the diet as well as the KAs or the placebo to the patients. OUTCOME MEASURES: Changes in GFR and renal and nutritional parameters were measured. RESULTS: Mean (+/- SD) GFR measured by the 99mTc-DTPA (99 m technetium diethylenetri-aminepenta-aceticacid) plasma sample method was unchanged in the ketodiet group: 28.1 +/- 8.8 (before) and 27.6 +/- 10.1 mL/min/1.73 m2 (after the study) (P =.72). However, it significantly decreased from 28.6 +/- 17.6 to 22.5 +/- 15.9 mL/min/1.73 m2 in the placebo group (P =.015). Serum creatinine before and after the study in the ketodiet group was 2.26 +/- 1.03 mg/dL and 2.07 +/- 0.8 mg/dL (P =.90) and in the placebo group was 2.37 +/- 0.85 and 3.52 +/- 2.9 mg/dL (P =.066), respectively. In both groups the mean BMI did not change from 25.4 +/- 4.2 to 24.5 +/- 4.2 kg/m2 (P =.46) for ketodiet and from 25.0 +/- 6.8 to 23.9 +/- 4.1 kg/m2 (P =.39) for the placebo group. Serum total proteins decreased significantly (P =.038) in the placebo group, and serum albumin showed a trend (P =.061) toward reduction, whereas both of these parameters were maintained in the ketodiet group. CONCLUSION: Over a 9-month period, very low-protein diet supplemented with ketoanalogs helped CRF patients to preserve GFR and maintain BMI. KAs were safe and efficacious in retarding the progression of renal failure and preserving the nutritional status of CRF patients.