Quantifying midbrain serotonin transporter in depression: a preliminary study of diagnosis and naturalistic treatment outcome.

INTRODUCTION: Serotonin may play an important role in the pathology of major depressive disorder (MDD). However, the relationship between serotonin transporter (SERT) availability and the medical outcome of antidepressant treatment is uncertain. METHODS: In this naturalistic study, SERT availability (expressed as the specific uptake ratio, SUR) in the midbrain of 17 drug-free patients with MDD and 17 controls matched for age and gender was measured using SPECT with [(123)I]ADAM. The severity of MDD was measured by the Hamilton Depression Rating Scale before, and after 6 weeks of non-standardized antidepressant treatment. RESULTS: A total of 12 patients completed the study. The SUR of the patients with MDD was significantly lower than that of the healthy controls. The SUR of SERT was not found to have a linear relationship with the treatment outcome; however, supplemental analysis found a curvilinear relationship between treatment outcome and the SUR of SERT. DISCUSSION: The findings indicate that the SUR of SERT is lower in patients with MDD; however it did not predict treatment outcome in a linear fashion. Studies with larger sample sizes are required.

The correlation between mid-brain serotonin transporter availability and intelligence quotient in healthy volunteers.

PURPOSE: This study was performed to investigate the association between the mid-brain serotonin transporter (SERT) availability and intelligence quotient (IQ). METHODS: One hundred and thirteen healthy participants, including 52 male and 61 female subjects, were recruited. We used SPECT with [(123)I]ADAM images to determine the SERT availability in the mid-brain, and measured the subjects' IQ using the WAIS-R. RESULTS: We found a significant positive correlation between the mid-brain SERT availability and the IQ of the participants. Even when controlling for age and sex, the significant association still existed. CONCLUSION: This result implied that the higher the SERT binding in the mid-brain, the better the IQ in healthy participants.

Lower availability of midbrain serotonin transporter between healthy subjects with and without a family history of major depressive disorder - a preliminary two-ligand SPECT study.

PURPOSE: Serotonin transporter (SERT) and dopamine transporter (DAT) levels differ in patients with major depressive disorder (MDD) who are in a depressed state in comparison with healthy controls. In addition, a family history of depression is a potent risk factor for developing depression, and inherited vulnerability to serotonergic and dopaminergic dysfunction is suspected in this. The aim of this study was to examine the availabilities of midbrain SERT and striatal DAT in healthy subjects with and without a first-degree family history of MDD. METHODS: Eight healthy subjects with first-degree relatives with MDD and 16 sex- and age-matched healthy controls were recruited. The availabilities of SERT and DAT were approximated using SPECT, employing [¹²³I] 2-((2-((dimethylamino) methyl) phenyl)thio)-5-iodophenylamine (ADAM) and [(99m)Tc] TRODAT-1 as the ligands, respectively. There are missing data for one participant with a first-degree family history of MDD from the ADAM study, due to a lack of the radio-ligand at the time of experiment. RESULTS: SERT availability in the midbrain was significantly lower in subjects with a first-degree family history of MDD than in healthy subjects. However, DAT availability was no different between two groups. CONCLUSIONS: The results with regard to the midbrain SERT level suggest the heritability of MDD.

Hypoxia imaging predicts success of hypoxia-induced cytosine deaminase/5-fluorocytosine gene therapy in a murine lung tumor model.

Tc-99m-HL91 is a hypoxia imaging biomarker. The aim of this study was to investigate the value of Tc-99m-HL91 imaging for hypoxia-induced cytosine deaminase (CD)/5-fluorocytosine (5-FC) gene therapy in a murine lung tumor model. C57BL/6 mice were implanted with Lewis lung carcinoma cells transduced with the hypoxia-inducible promoter-driven CD gene (LL2/CD) or luciferase gene (LL2/Luc) serving as the control. When tumor volumes reached 100 mm(3), pretreatment images were acquired after injection of Tc-99m-HL91. The mice were divided into low and high hypoxic groups based on the tumor-to-non-tumor ratio of Tc-99m-HL91. They were injected daily with 5-FC (500 mg kg(-1)) or the vehicle for 1 week. When tumor volumes reached 1000 mm(3), autoradiography and histological examinations were performed. Treatment with 5-FC delayed tumor growth and enhanced the survival of mice bearing high hypoxic LL2/CD tumors. The therapeutic effect of hypoxia-induced CD/5-FC gene therapy was more pronounced in high hypoxic tumors than in low hypoxic tumors. This study provides the first evidence that Tc-99m-HL91 can serve as an imaging biomarker for predicting the treatment responses of hypoxia-regulated CD/5-FC gene therapy in animal tumor models. Our results suggest that hypoxia imaging using Tc-99m-HL91 has the predictive value for the success of hypoxia-directed treatment regimens.

The use of dual-phase 18F-FDG PET in characterizing thyroid incidentalomas.

AIM: To examine the usefulness of dual-phase 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) for the evaluation of thyroid incidentalomas. MATERIALS AND METHODS: In this retrospective study, cases with focal thyroid lesions seen incidentally at FDG PET in which the histopathological diagnosis was available and in which dual-phase FDG PET imaging was performed at 1 and 2 h after FDG injection were reviewed. In the included cases, the 1 and 2 h maximal standard uptake value (1-hour maximal SUV and 2-hour maximal SUV, respectively) and retention index (RI) were calculated, and the differences between benign and malignant thyroid incidentalomas were analysed. Receiver operating characteristic (ROC) analysis was performed to evaluate the ability of 1-hour maximal SUV, 2-hour maximal SUV, and RI to discriminate benign from malignant lesions. RESULTS: A total of 39 patients (25 females, 14 males) with 45 lesions (17 malignant, 28 benign) were included. In malignant thyroid incidentalomas, the average 1-hour maximal SUV, 2-hour maximal SUV, and RI were 5.20, 5.72, and 7.67%, respectively, and in benign thyroid incidentalomas the values were 4.67, 4.97, and 7.38%, respectively. There were no significant differences in 1-hour maximal SUV, 2-hour maximal SUV, and RI between benign and malignant lesions. The area under the ROC curve did not differ from 0.5. CONCLUSION: Dual-phase FDG PET is not useful for differentiating benign from malignant thyroid incidentalomas.

Clinical significance and outcome of one or two rib lesions on bone scans in breast cancer patients without known metastases.

The presence of one or two rib lesions on bone scans of post-treatment breast cancer patients without known metastases often makes clinical decision making problematic. The aim of this study was to identify skeletal metastasis predictors that might help the management of these patients. We recruited post-treatment breast cancer patients without overt metastases whose bone scans showed (1) one or two rib hot spots, or (2) one rib lesion and a concurrent bone abnormality. Their clinical and serial scintigraphic data were collected, reviewed and evaluated for correlations. After their first abnormal bone scans, 23 patients (11 of the 77 patients initially with one rib lesion (incidence, 14.3%), three of the 27 patients with two rib lesions (incidence, 11.1%), and nine of the 11 patients with one rib lesion plus a concurrent bone abnormality (incidence, 81.8%)) developed multiple bone metastases within 2 years of the initial rib lesions in all but one case. Univariate analyses revealed that a concurrent bone lesion other than the rib, direct tumour invasion to the chest wall or skin, and 10 or more lymph nodes involved were associated with increased risks of bone metastases whereas longer persistence of the rib lesions was associated with a lower risk. Multivariate proportional hazard analyses indicated that patients with a concurrent bone lesion other than the rib (relative risk (RR)=39.65; 95% confidence interval (CI)=8.13-193.28), 10 or more lymph nodes involved (RR=13.49; 95% CI=2.09-86.91), and no radiotherapy (RR=7.59; 95% CI=2.11-27.39) were more likely to have bone metastases, while those with longer persistence of the rib lesions (RR=0.92; 95% CI=0.84-0.98) and longer time interval between surgery and the rib lesion detection (RR=0.96; 95% CI=0.94-0.99) were less likely. We have identified clinical features applicable to risk stratification. High incidence of bone metastases was noted in patients with one rib lesion and a concurrent bone abnormality. Regular follow-up for 2 years after detection of rib lesions is recommended, especially for those with risk factors.

Evolution of differential renal function after acute pyelonephritis.

(99m)Tc dimercaptosuccinic acid (DMSA) renal scans can provide accurate diagnosis of acute pyelonephritis, its sequelae (renal scars) and differential renal function (DRF). The purposes of this retrospective study were (1) to assess the relationship between DRF obtained during acute pyelonephritis and at follow-up, and (2) to elucidate the value of initial DRF in predicting subsequent renal scars. A total of 47 children were enrolled. All had both unilateral acute pyelonephritis diagnosed by initial DMSA renal scans, and follow-up DMSA renal scans. We found the correlation between initial and follow-up DRF poor (adjusted R2 = 0.396). Whether or not renal scars developed determined the follow-up DRF. Vesicoureteral reflux was significantly more common in children who developed renal scars. In addition, the higher the grade of vesicoureteral reflux, the lower the follow-up DRF and the improvement in DRF. When using a DRF of 46% as the cut-off value to predict subsequent renal scars, the sensitivity and specificity were 47.8% and 83.3%, respectively. Owing to the low sensitivity, initial DRF is not suitable for predicting the occurrence of renal scars.

Renal fibrosis: prediction from acute pyelonephritis focus volume measured at 99mTc dimercaptosuccinic acid SPECT.

PURPOSE: To evaluate whether acute pyelonephritis lesion volume derived from acute technetium 99m ((99m)Tc) dimercaptosuccinic acid (DMSA) renal single photon emission computed tomographic (SPECT) images is predictive of the development of subsequent renal fibrosis. MATERIALS AND METHODS: Children with acute pyelonephritis underwent (99m)Tc DMSA renal SPECT during acute infection and 6-10 months later. At quantitative analysis, the volume of photopenic lesions and the ratio of radioactivity in the photopenic lesion to that in normal renal tissue were calculated. Sensitivity, specificity, and positive and negative predictive values were determined. RESULTS: Sixty-nine acute pyelonephritis foci in 44 children were analyzed. Thirty-seven (54%) of these lesions were normal on follow-up renal scans, while 32 (46%) developed scars. Significant differences in the photopenic lesion volume were found between the two groups (P < .001). When photopenic lesion volume indicated a positive diagnosis (>or=4.6-cm(3) lesion volume), sensitivity, specificity, positive predictive, and negative predictive values were 96.7%, 92.3%, 90.6%, and 97.3%, respectively. CONCLUSION: Quantitative analysis of acute DMSA renal SPECT findings is valuable in predicting renal fibrosis. The volume of an acute pyelonephritis lesion is useful in predicting the development of fibrosis.

Alzheimer's disease: scintigraphic appearance of Tc-99m HMPAO brain spect.

UNLABELLED: To investigate the value of Tc-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) single photon emission computed tomography (SPECT) as a diagnostic test for Alzheimer's disease. METHODS AND PATIENTS: Tc-99m HMPAO SPECT was performed on 140 patients and 20 controls. A final diagnosis was established for 115 patients, 58 of whom had Alzheimer's disease. The probability of AD was determined for seven scintigraphic patterns. The probability of Alzheimer's disease was 14% for patients with memory loss and normal perfusion. For patients with abnormal perfusion patterns, the probability of Alzheimer's disease was 87% with bilateral temporoparietal defects, 73% with bilateral temporoparietal defects plus additional defects, 62% with a unilateral temporoparietal defect, 33% with a frontal defect only, 0% with other large defects, and 0% with multiple small cortical defects. In 115 patients with the complaint of memory loss or cognitive abnormalities, bilateral temporoparietal hypoperfusion with or without additional hypoperfusion was more frequent than other scintigraphic patterns in patients with Alzheimer's disease. Tc-99m HMPAO SPECT offers the clinician the possibility of differentiating dementias on the basis of differences in perfusion patterns.

Differential changes in regional bone mineral density in healthy Chinese: age-related and sex-dependent.

To investigate the pattern of age-related and sex-dependent bone mineral density (BMD) changes in the six skeletal regions in healthy Chinese, total-body and regional BMD were measured by dual-energy X-ray absorptiometry (DXA) in 310 women and 387 men aged 20-80 years. In women, a five-phase change was discernible in the axial bones: (1) gradual bone increase from 20-29 years old to maximal BMD at 35-39 years old; (2) maintenance of this level from 35-39 to 40-44; (3) a mild bone decrease from 40-44 to 45-49; (4) a rapid bone decrease from 45-49 to 55-59; and (5) a decelerated bone decrease after 55-59 years old. After validation of menopause status, the decrease of BMD in the late 40s became insignificant in premenopausal women. In appendicular bones, no obvious peak was observed, and significant bone decrease started at 50-54 years old. The overall bone decrease from 35-39 to 70-80 years old was 19.3% for the total body, 16.4% for the head, 29% for the spine, 23% for the pelvis, 18.2% for the ribs, 23.9% for the arms, and 20.4% for the legs. In men, the maximal bone mass was attained at 30-34 and 35-39 years old for axial and appendicular bones, respectively. The age-related bone decrease in the skeletal regions was small, except from 60-64 to 65-69 years old. The overall bone decrease in each region from maximal bone mass to 70-80 years old was 6.7% for the total body, 1.7% for the head, 7.6% for the spine, 11.3% for the pelvis, 9.5% for the ribs, 7.8% for the arms, and 10.4% for the legs. The overall magnitude of reduction in total-body BMD in women was about three times greater than that in men. The pattern of BMD changes differs in each region and is age-related as well as sex-dependent. There appeared to be no significant premenopausal bone decrease.

Use of 99mTc (V) DMSA scintigraphy in the detection and localization of intestinal inflammation: comparison of findings and colonoscopy and biopsy.

PURPOSE: To evaluate the potential use of technetium 99m (99mTc) (V) dimercaptosuccinic acid (DMSA) scintigraphy in the detection and localization of intestinal inflammation. MATERIALS AND METHODS: In a prospective study, 62 patients who were suspected of having intestinal inflammation and 30 control subjects were enrolled. All patients underwent 99mTc (V) DMSA scintigraphy and colonoscopy with biopsy within 1 week. 99mTc (V) DMSA scintigrams were interpreted blindly with respect to clinical information, and radiotracer uptake in the bowel segments was graded. The findings were then compared with the results of the colonoscopy and colonoscopic biopsy. RESULTS: In the detection of intestinal inflammation, findings at 99mTc (V) DMSA scintigraphy were as follows: true-positive in 55, false-positive in two, true-negative in 32, and false-negative in three. Overall sensitivity was 95%; overall specificity, 94%; and overall accuracy, 95%. CONCLUSION: Our results show that 99mTc (V) DMSA scintigraphy is a useful noninvasive diagnostic test for the detection and localization of intestinal inflammation.

Clinicopathologic correlation of serum tissue polypeptide specific antigen in hepatocellular carcinoma.

OBJECTIVE: Recently, tissue polypeptide specific antigen (TPS) has been introduced as a cell proliferation marker. Little is known about its clinical significance in hepatocellular carcinoma (HCC). This study aimed to clarify serum TPS levels and tumor invasiveness of HCC. METHODS: Serum TPS levels were determined with a monoclonal TPS IRMA assay in 69 patients with HCC. A correlation between serum TPS levels and clinical, biochemical, and pathological features was sought and compared with that of alpha-fetoprotein (AFP). In 57 healthy subjects, 56 patients with biopsy-proven chronic hepatitis and in 49 patients with liver cirrhosis, serum TPS levels were assayed and compared. RESULTS: Serum TPS levels were significantly correlated with glutamic oxalacetic transaminase (p < 0.0001), glutamic pyruvic transaminase (p < 0.001), and lactate dehydrogenase (p = 0.027). There tended to be a positive relationship between serum TPS levels and tumor size, histological differentiation, capsular invasion, portal invasion, and clinical staging, although it did not reach statistical significance. A significant correlation, however, was observed between AFP and tumor size (p = 0.01), number (p = 0.042), histological grading (p = 0.028), portal invasion (p = 0.009), and clinical staging (p = 0.03). Patients with HCC had significantly higher TPS than healthy subjects (p < 0.001). However, there was substantial overlap between patients with HCC, chronic hepatitis, and liver cirrhosis. CONCLUSIONS: Our data suggest that serum TPS is not significantly related to tumor invasiveness in patients with HCC. Serum TPS levels are affected by the proliferative activity of the underlying chronic liver disease, which is frequently associated with HCC in Chinese patients. As a cell proliferation marker, serum TPS should be interpreted cautiously in the presence of chronic liver disease.

Role of beta 2-microglobulinuria and microalbuminuria in pediatric febrile urinary tract infection.

Urinary beta-2-microglobulin (beta 2M) and microalbumin concentrations were analyzed in 61 pediatric patients with febrile urinary tract infection (UTI). The results were compared with those of technetium-99m-labeled dimercaptosuccinic acid (99mTc-DMSA) single photon emission computed tomography (SPECT) imaging. Noninvasive evaluations were made to localize the site of the UTI. Increased urinary beta 2M/Creatinine (Cr) or microalbumin/Cr quotients were not associated with renal inflammation, as defined by a positive renal scan. Increased urinary microalbumin/Cr is associated with UTI in febrile patients regardless of the level of infection (scan status), and may be an informative indicator of UTI. When microalbumin/Cr was > or = 0.03, its sensitivity and specificity to predict UTI in febrile patients, regardless of the site of the infection, were 95.65% and 51.79%, respectively, and its positive predictive value was 62.0%. On the other hand, urinary beta 2M/Cr (> or = 0.13) demonstrates a statistically significant correlation with the presentation of a high grade of vesicoureteral reflux (p = 0.02). We suggest that a prompt renal imaging study is warranted when the urinary beta 2M/Cr ratio is high (> or = 0.13).

Heroin-induced rhabdomyolysis as a cause of reflex sympathetic dystrophy.

Reflex sympathetic dystrophy is an excessive or abnormal response of the sympathetic nervous system in an extremity to an injury or other condition. The authors describe a 37-year-old man who experienced constant pain and vasomotor instability in both feet after nontraumatic rhabdomyolysis secondary to smoking heroin. Three-phase bone scintigraphy was performed and revealed significantly increased blood-flow, blood-pool, and delayed-phase radioactivity. The follow-up three-phase bone scinitigram showed less radiotracer uptake that was consistent with a good response to calcitonin therapy. Heroin-induced rhabdomyolysis should be added to the list of precipitating conditions that can induce this syndrome.

Differences in 99mTc-HMPAO brain SPET perfusion imaging between Tourette's syndrome and chronic tic disorder in children.

Early differential diagnosis between Tourette's syndrome and chronic tic disorder is difficult but important because both the outcome and the treatment of these two childhood-onset diseases are distinct. We assessed the sensitivity and specificity of brain single-photon emission tomography (SPET) perfusion imaging in distinguishing the two diseases, and characterized their different cerebral perfusion patterns. Twenty-seven children with Tourette's syndrome and 11 with chronic tic disorder (mean age 9.5 and 8.6 years, respectively) underwent brain SPET with technetium-99m hexamethylpropylene amine oxime (HMPAO). Visual interpretation and semiquantitative analysis of SPET images were performed. On visual interpretation, 22 of 27 (82%) of the Tourette's syndrome group had lesions characterized by decreased perfusion. The left hemisphere was more frequently involved. None of the children with chronic tic disorder had a visible abnormality. Semi-quantitative analysis showed that, compared with children with chronic tic disorder, children with Tourette's syndrome had significantly lower perfusion in the left lateral temporal area and asymmetric perfusion in the dorsolateral frontal, lateral and medial temporal areas. In conclusion, using the visual approach, brain SPET perfusion imaging is sensitive and specific in differentiating Tourette's syndrome and chronic tic disorder. The perfusion difference between the two groups, demonstrated by semi-quantitative analysis, may be related more to the co-morbidity in Tourette's syndrome than to tics per se.

Protein-losing enteropathy: diagnosis with (99m)Tc-labeled human serum albumin scintigraphy.

PURPOSE: To investigate the diagnostic value of technetium 99m-labeled human serum albumin (HSA) scintigraphy in a group of patients suspected of having protein-losing enteropathy (PLE). MATERIALS AND METHODS: After intravenous injection of 740 MBq of freshly prepared (99m)Tc HSA, serial images of the abdomen were obtained from 10 minutes until 24 hours after injection. A (99m)Tc HSA scan was considered positive for PLE if there was visible tracer exudation in the gut. The diagnosis was established on the basis of standard clinical and biopsy findings. RESULTS: Thirty-nine scans were obtained: 27 scans in 26 suspected cases of PLE and 12 scans in control subjects with no known gastrointestinal disease. Twenty-five of the 26 studies in patients suspected of having PLE showed (99m)Tc HSA activity in the bowel. Among the 25 studies with positive findings, seven demonstrated PLE only on images obtained 24 hours after injection. In the control subjects, no activity was seen in the bowel. CONCLUSION: (99m)Tc HSA with serial scanning for up to 24 hours is reliable and useful for imaging PLE. Sites of protein loss may also be demonstrated. This imaging method is convenient, easy to perform, and yields results within 24 hours.

Synchronous pyomyositis and septic hip arthritis.

The authors report a rare concomitant pyogenic infection of the iliopsoas, iliacus and external obturator muscles and of the hip joint in a 68-year-old woman. Because the patient showed the classic symptomatic triad of limping, hip pain and fever, in addition to positive hip arthrocentesis, the diagnosis of septic hip arthritis was routine, but the simultaneous pyomyositis was almost overlooked. Unusual localised heat and swelling on the front of the proximal thigh prompted a CT scan that identified remarkable muscle abscesses in addition to the septic arthritis. Surgical debridement and antibiotics resolved the infection relatively rapidly without sequelae. We noted that reaching a definitive diagnosis of such a concomitant infection requires a suspicion of the presence of pyomyositis, which can be definitively determined using advanced imaging studies.

Symptomatic and asymptomatic accessory navicular bones: findings of Tc-99m MDP bone scintigraphy.

AIM: The accuracy of bone scintigraphy in diagnosing symptomatic accessory navicular bones has not been well studied. We conducted a retrospective study to explore the results and use of scintigraphy in symptomatic and asymptomatic accessory navicular bones. MATERIALS AND METHODS: Thirteen patients with a total of 13 symptomatic and 10 asymptomatic accessory navicular bones were included in the study. We used a scoring system to grade the scintigraphic abnormalities. The patients' symptoms and scintigraphic findings were recorded. RESULTS: Though focally increased radiopharmaceutical uptake was observed in all symptomatic accessory naviculars, half of the asymptomatic accessory navicular bones had the same manifestations. The scoring system was of no value in differentiating symptomatic from asymptomatic accessory navicular bones. CONCLUSION: Bone scintigraphy is a sensitive but not a specific tool for diagnosing a symptomatic accessory navicular.

Peritoneal scintigraphy for diagnosing periumbilical leakage in a patient on continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) offers several advantages over hemodialysis for patients with end-stage renal disease; however, this technique also includes many documented complications. A case with clinical suspicion of dialysate leakage on CAPD was investigated by peritoneal scintigraphy using technetium-99m macroaggregated human albumin (99mTc-MAA). Peritoneal scintigraphy showed radiotracer accumulation over the periumbilical area at 2 hours 30 minutes after intraperitoneal infusion of 99mTc-MAA. Six hours of imaging revealed more apparent radioactivity at the same site. This study is to illustrate the simple diagnostic helpfulness of peritoneal scintigraphy in a patient with a CAPD-related structural defect.