Radiosynoviorthesis in hemophilic arthropathy: pathologic blood pool imaging on pre-therapeutic bone scintigraphy is not a predictor of treatment success.

PURPOSE: Increased articular 99mTc MDP uptake on blood pool imaging (BPI) of patients with rheumatologic conditions is indicative of active inflammatory changes, and has been suggested as a strong predictor of response to radiosynoviorthesis (RSO). In this study, we aimed to assess the value of pretreatment BPI positivity (i.e. scintigraphic-apparent hyperemia) for successful RSO in hemophilic arthropathy. METHODS: Thirty-four male patients with painful hemophilic arthropathy underwent RSO after failure of conservative treatment. Treated joints comprised the knee in eight, elbow in five, and ankle in 21 patients. Pretreatment triple-phase bone scintigraphy showed hyperemic joints (pathologic BPI) in 17 patients, whereas 17 patients had no increased tracer uptake on BPI. Response to RSO was evaluated 6 months post-treatment by measuring changes in intensity of arthralgia according to the visual analog scale (VAS), bleeding frequency, and range of motion. The association between hyperemia (pathologic BPI) and treatment outcome was examined using nonparametric tests for independent samples. RESULTS: Clinically evident pain relief occurred in 26 patients (76.5 %), and the mean VAS decreased from 7.7 ± 1.1 to 4.6 ± 2.7 (p < 0.001). Joint bleeding frequency (hemarthrosis) decreased from 4.5 ± 0.6 to 2.1 ± 0.4 during the first 6 months after RSO (p < 0.001). For both parameters (pain relief and bleeding frequency), patients experienced a similar benefit from RSO regardless of pretreatment BPI: arthralgia (p = 0.312) and frequency of hemarthrosis (p = 0.396). No significant improvement was observed for range of motion, but it was significantly more restricted in hyperemic joints both before (p = 0.036) and after treatment (p = 0.022). CONCLUSIONS: Hemophilic arthropathy can be effectively treated with RSO regardless of pre-therapeutic BPI. Patients in whom articular hyperemia is not detectable by scintigraphy may have similar (outstanding) outcomes, and thus should not be excluded from treatment.

Prospective use of subtraction ictal SPECT coregistered to MRI (SISCOM) in presurgical evaluation of epilepsy.

PURPOSE: In patients with drug-refractory focal epilepsy, nonlesional magnetic resonance imaging (MRI) or discordant data of presurgical standard investigations leads to failure generating a sufficient hypothesis for electrode implantation or epilepsy surgery. The seizure-onset zone can be further investigated by subtraction ictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM). This is an observational study of a large consecutive cohort of patients undergoing prospective SISCOM to generate hypothesis for electrode implantation or site of epilepsy surgery. METHODS: One hundred seventy-five consecutive patients undergoing presurgical evaluation with either nonlesional MRI or discordant data of standard investigations preventing the generation of hypothesis for seizure onset were evaluated with SISCOM. Results were compared to gold standard for seizure onset detection, either electrocorticography (ECoG) and/or postoperative outcome. KEY FINDINGS: One hundred thirty patients had successful SPECT injection. Hypothesis for electrode implantation/site of surgery was generated in 74 patients. Forty patients had gold standard comparison. Twenty-eight patients underwent resective surgery. SISCOM was concordant to site of surgery in 82%. An additional 12 patients underwent invasive EEG monitoring but were not suitable for surgery. SISCOM was concordant multifocal in 75%. Two years postsurgical follow-up of 26 patients showed favorable outcome in 22 (Engel class I and class II). SIGNIFICANCE: SISCOM is a highly valuable diagnostic tool to localize the seizure-onset zone in nonlesional and extratemporal epilepsies. Outcome in this patient group was unexpectedly good, even in patients with nonlesional MRI. The high correlation with ECoG and site of successful surgery is a strong indicator that outcome prediction in this patient group should be adapted accordingly, which may encourage more patients to undergo electrode implantation and subsequent successful surgery. Statistical analysis showed that SISCOM with shorter duration of seizures, focal seizures, and lesional MRI was more likely to generate implantation hypothesis.

Influence of 5-HTTLPR polymorphism on resting state perfusion in patients with major depression.

Neuroimaging studies in major depressive disorder (MDD) have indicated dysregulation in a network involving prefrontal cortex, subgenual cingulate and the amygdalae, which is known to be modulated by serotonin. The serotonergic system is the principal target for pharmacological treatment in MDD and the functional variable serotonin promoter polymorphism (5-HTTLPR) influences susceptibility, course and treatment response of MDD. Using data from a previously published sample of 89 MDD-patients, we examined post hoc the effect of 5-HTTLPR status on resting state perfusion, as measured with (99m)Tc-HMPAO-SPECT. MDD patients were stratified according to receptor polymorphism, both using a bi-allelic (group A: L/L vs. group B: S/S and S/L genotype) and a tri-allelic approach (Group A': LA/LA vs. Group B': non-LA/LA genotype). There were no significant differences between both subgroups regarding age, gender, severity of depression, medication, or treatment response (p > 0.1). Using the bi-allelic approach, Group B, compared to group A, revealed a significantly higher resting state perfusion in medial prefrontal cortex (p(voxel) (FWE) < 0.05). Additional ROI analyses showed relative overactivity of the amygdalae in group B (p(voxel) (FWE) < 0.05). Similar effects were observed in the tri-allelic approach. The opposite contrasts (Group A > Group B) revealed no significant effects. We demonstrate that in patients with MDD, 5-HTTLPR gene polymorphism modulates resting state perfusion in key structures of mood processing. While the clinical impact of these findings will need to be further investigated in larger cohort studies, the necessity to monitor and to account for individual 5-HTTLPR-status in future MDD imaging studies is highly recommended.

The value of HMPAO SPECT in predicting treatment response to citalopram in patients with major depression.

Alterations of regional cerebral blood flow (rCBF) in prefrontal cortex and the anterior cingulate cortex are conspicuous imaging findings in patients with major depression (MD). While these rCBF changes have been suggested as functional disease markers, data in large patient samples examining treatment response prediction to antidepressant therapy are limited. This study examined the predictive value of Tc-99m-HMPAO-SPECT for subsequent treatment response to antidepressant therapy with citalopram in an unprecedented large collective of patients. Ninety-three patients with MD were examined with Tc-99m-HMPAO-SPECT twice, at the beginning of citalopram-treatment (T1) and after 4 weeks of treatment (T2). To determine the impact of rCBF changes associated with treatment response, the patient sample was divided into two subgroups: responders (44 patients) and non-responders (49 patients). A two-sample t-test was used to determine group-specific rCBF-differences. Age, gender and initial Hamilton Rating Scale for Depression (HRSD) were treated as regressors of no interest. The responder group revealed significant relative rCBF increases at T1 in a large region en-compassing predominantly prefrontal and temporal cortices as well as subgenual cingulate cortex. No relative rCBF decreases were detected in this group. The comparison between T1 and T2 revealed trends of rCBF decreases in inferior frontal gyrus and rCBF increases in premotor cortex in the responder group. Our data show that rCBF measurements with TC-99M-HMPAO-SPECT provide a predictor estimate for subsequent treatment response in depressed patients undergoing antidepressant therapy with citalopram. This effect is highly significant and, most notably, independent of the initial HRSD score.

Response-dependent differences in regional cerebral blood flow changes with citalopram in treatment of major depression.

UNLABELLED: Major depression (MD) is the most frequent psychiatric disorder with a predicted increase within the next decade. The understanding of the neurobiologic basis of its cause, antidepressive treatment effects, and identification of treatment outcome predictors is of crucial importance to warrant efficient medical care. The aim of our study was to investigate differences of regional cerebral blood flow (rCBF) in MD between responders and nonresponders in the beginning and differences during the course of treatment. METHODS: 99mTc-Labeled d,l-hexamethylpropyleneamine oxime brain scans under resting conditions were performed on 65 patients with MD. All patients were treated with citalopram as an antidepressive monotherapy. SPECT scans were performed 2 times, at the beginning (t1) and after 4 wk of medication (t2). Voxel-by-voxel analyses were performed using SPM. Unpaired t test, paired t test, and multigroup analysis were used on a significance threshold of P < 0.005 (uncorrected) to identify significant differences in rCBF between responders and nonresponders at t1, within both groups over time of treatment (t2-t1), as well as a group x time interactions. RESULTS: Thirty-five patients responded after 4 wk of treatment. Distinct differences between responders and nonresponders were found at the beginning of treatment and also relating to changes in rCBF during treatment. Responders showed a higher posterior cingulate activity at t1. Furthermore, an opposite direction of rCBF changes during treatment could be observed in this area. CONCLUSION: The differences in rCBF in responders and nonresponders in the posterior cingulate at t1 and the opposite directed changes in rCBF in both groups during treatment in this region suggest that the posterior cingulate function plays a key role in the pathophysiology of depression and may have a predictive value for antidepressive treatment outcome.

Integrated PET/CT in differentiated thyroid cancer: diagnostic accuracy and impact on patient management.

UNLABELLED: The aim of this study was to investigate the diagnostic accuracy and impact on patient management of the new integrated PET/CT modality in patients with suspected iodine-negative, differentiated thyroid carcinoma (DTC). METHODS: Forty patients with DTC and a suggestion of iodine-negative tumor tissue underwent PET/CT examination (370 MBq (18)F-FDG, coregistered PET/CT whole-body images). As the first step of analysis, PET and CT images were scored blindly and independently by 2 nuclear medicine physicians and 2 radiologists. A 5-point scale was used. The second step consisted of a consensus reading, during which a virtual side-by-side fusion of PET and CT images was initially evaluated and afterward the "real" fusion (i.e., coregistered) PET/CT images were also scored with the same 5-point scale. The imaging results were compared with histopathologic findings and the course of disease during further follow-up examinations. RESULTS: One hundred twenty-seven lesions in 40 patients were evaluated. Diagnostic accuracy was 93% and 78% for PET/CT and PET, respectively (P = 0.049, per-patient analysis). In 17 (74%) of 23 patients with suspicious (18)F-FDG foci, integrated PET/CT added relevant information to the side-by-side interpretation of PET and CT images by precisely localizing the lesion(s). In tumor-positive PET patients, PET/CT fusion by coregistration led to a change of therapy in 10 (48%) patients. Futile surgery was prevented in an additional 3 patients. CONCLUSION: Integrated PET/CT is able to improve diagnostic accuracy in a therapeutically relevant way in patients with iodine-negative DTC. By precisely localizing tumor tissue, image fusion by integrated PET/CT is clearly superior to side-by-side interpretation of PET and CT images.

Diagnostic performance of whole body dual modality 18F-FDG PET/CT imaging for N- and M-staging of malignant melanoma: experience with 250 consecutive patients.

PURPOSE: To assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) using (18)F-fluorodeoxyglucose (FDG) for N- and M-staging of cutaneous melanoma. PATIENTS AND METHODS: This is a retrospective and blinded study of 250 consecutive patients (105 women, 145 men; age 58 +/- 16 years) who underwent FDG-PET/CT for staging of cutaneous melanoma at different time points in the course of disease. Whole-body FDG-PET/CT was performed 101 +/- 21 minutes postinjection of 371 +/- 41 MBq FDG. Diagnostic accuracy for N- and M-staging was determined for CT alone, PET alone, and PET/CT. RESULTS: PET/CT detected significantly more visceral and nonvisceral metastases than PET alone and CT alone (98.7%, 88.8%, and 69.7%, respectively). PET/CT imaging thus provided significantly more accurate interpretations regarding overall N- and M-staging than PET alone and CT alone. Overall N- and M-stage was correctly determined by PET/CT in 243 of 250 patients (97.2%; 95% CI, 95.2% to 99.4%) compared with 232 patients (92.8%; 95% CI, 89.6% to 96.0%) by PET, and 197 patients (78.8%; 95% CI, 73.7% to 83.9%) by CT. All differences were significant. Accuracy of PET/CT was significantly higher than that of PET and CT for M-staging (0.98 v 0.93 and 0.84) and significantly higher than that of CT for N-Staging (0.98 v 0.86). Change of treatment according to PET/CT findings occurred in 121 patients (48.4%). CONCLUSION: The diagnostic performance of FDG-PET/CT for N- and M-staging of melanoma patients suggests its use for whole-body tumor staging, especially for detection or exclusion of distant metastases.

PET recognition of pulmonary metastases on PET/CT imaging: impact of attenuation-corrected and non-attenuation-corrected PET images.

PURPOSE: The aims of this study were to assess the performance of FDG PET at PET/CT imaging for the detection of pulmonary metastases and to evaluate differences in lesion detectability on attenuation-corrected (AC) and non-attenuation corrected (NAC) PET images. METHODS: The institutional PET/CT database was searched for patients with pulmonary metastases of 3-60 mm in diameter. Ninety-two patients with 438 metastases to the lungs were included in the study. The primary tumours were 33 malignant melanomas, 12 carcinomas of unknown primary, 11 colorectal carcinomas, eight differentiated thyroid carcinomas, seven aggressive non-Hodgkin's lymphomas, six head and neck cancers, three breast cancers, two prostate cancers and ten others. Lesion detectability was visually compared between PET and CT and between AC and NAC PET images using a five-point scale. RESULTS: Of the 438 pulmonary metastases, 174 were detected with FDG PET (39.7%), six of them on NAC images only (not significant). Visual scores were higher on NAC images in 41.4% and equal in 54.6% of lesions. The sensitivity of FDG PET increased significantly from 0.405 for metastases of 5-7 mm in diameter to 0.784 for lesions of 8-10 mm and to 0.935 for lesions measuring 11-29 mm in diameter. No metastases smaller than 5 mm in diameter were seen on PET images. CONCLUSION: FDG PET/CT is useful for the assessment of pulmonary metastases. The frequency of lesion detection is similar for AC and NAC PET images. A reduced sensitivity of FDG PET has to be considered for lesions smaller than 11 mm in diameter.

111In-pentetreotide and 123I-MIBG for detection and resection of lymph node metastases of a carcinoid not visualized by CT, MRI or FDG-PET.

A patient with a history of a jejunal carcinoid and resection of liver metastases underwent CT, MRI and FDG-PET as well as somatostatin receptor scintigraphy using 111In-pentetreotide during follow-up. Octreoscan demonstrated one extrahepatic abdominal lesion with pathologic uptake, while the other imaging modalities failed to show a corresponding abnormality. For verification of this finding 123I-MIBG scintigraphy was performed. The MIBG scan confirmed the octreotide positive lesion and showed an additional abdominal lesion in the SPECT study. According to the scintigraphic results, radioguided surgery (RGS) was implemented using 123I-MIBG. This resulted in the intra-operative detection of two para- and pre-aortic lymph node metastases by the gamma probe and successful resection. An additional preaortal lymph node, suspicious by palpation, was also removed. Histopathology revealed metastases of a carcinoid tumor in all three specimens. In conclusion, the use of RGS facilitates successful removal of carcinoid metastatic lesions despite negative conventional imaging results. Secondly, 123I-MIBG scintigraphy may provide advantages over octreoscan for preoperative localization as well as radio-guided surgery of neuroendocrine metastatic lesions, if the involved site is located in proximity to highly octreotide-avid organs such as the kidneys or spleen.

Detection of Klatskin's tumor in extrahepatic bile duct strictures using delayed 18F-FDG PET/CT: preliminary results for 22 patient studies.

UNLABELLED: Detection of cholangiocarcinoma in extrahepatic bile duct strictures is a continuing challenge in clinical practice because brush cytology taken at endoscopic retrograde cholangiography has an average sensitivity of 50%. The aim of this study was to evaluate the effectiveness of dual-modality PET/CT using (18)F-FDG for noninvasive differentiation of extrahepatic bile duct strictures. METHODS: Twenty-two PET/CT studies were performed on 20 patients (10 women, 10 men; mean age +/- SD, 63 +/- 14 y) with extrahepatic bile duct strictures on endoscopic retrograde cholangiography. PET imaging was started 101 +/- 22 min after injection of 369 +/- 48 MBq of 18F-FDG. Blood glucose was 100 +/- 20 mg/dL. PET images were reconstructed iteratively with attenuation correction based on a rescaling of the CT image. CT was performed within 1 min before the PET study, with the patient in the same position. CT was used to place a volume of interest 5 cm in diameter at the liver hilus for quantitative evaluation of PET images by means of standardized uptake values (SUVs). RESULTS: Final diagnosis was histologically proven cholangiocarcinoma in 14 cases and benign causes of strictures in 8 cases without evidence of malignancy during a follow-up of 18 +/- 3 mo. All patients with cholangiocarcinoma presented with focal increased uptake in the liver hilus with an SUV of 6.8 +/- 3.3 (range, 3.9-15.8), compared with 2.9 +/- 0.3 (range, 2.5-3.3) in patients with benign causes of strictures (P = 0.003). There was a clear cutoff SUV of 3.6 for detection of malignancy in the liver hilus. CONCLUSION: 18F-FDG PET/CT provided high accuracy for noninvasive detection of perihilar cholangiocarcinoma in extrahepatic bile duct strictures.

Nasolacrimal drainage obstruction after radioiodine therapy: case report and a review of the literature.

The authors report a 54-year-old woman with papillary thyroid carcinoma (Lindsay type, pT2 N0 M1) with pulmonary metastases. After a total thyroidectomy, a series of 3 radioiodine therapies were performed with a cumulative dose of 700 mCi I-131. After termination of the therapy, the patient was initially without complaints, but approximately 6 months later, epiphora was noted, first only of the right eye and eventually of both eyes. A whole-body I-131 scan performed 1 year after final radioiodine therapy showed atypical tracer accumulation in both medial orbital regions. This finding was new compared with the scan that was done 1 year before. Dacryocystography revealed bilateral occlusion of the lacrimal drainage system. A review of the literature shows that epiphora and lacrimal duct alterations are rarely investigated and potentially underestimated side effects after high-dose radioiodine therapy.

Correlation of hippocampal glucose oxidation capacity and interictal FDG-PET in temporal lobe epilepsy.

PURPOSE: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) demonstrates temporal hypometabolism in the epileptogenic zone of 60-90% of patients with temporal lobe epilepsy. The pathophysiology of this finding is still unknown. Several studies failed to show a correlation between hippocampal FDG-PET hypometabolism and neuronal cell loss. Because FDG is metabolized by hexokinase bound to the outer mitochondrial membrane, we correlated the glucose-oxidation capacity of hippocampal subfields obtained after surgical resection with the corresponding hippocampal presurgical FDG-PET activity. METHODS: In 16 patients with electrophysiologically confirmed temporal lobe epilepsy, we used high-resolution respirometry to determine the basal and maximal glucose-oxidation rates in 400-microm-thick hippocampal subfields obtained after dissection of human hippocampal slices into the CA1 and CA3 pyramidal subfields and the dentate gyrus. RESULTS: We observed a correlation of the FDG-PET activity with the maximal glucose-oxidation rate of the CA3 pyramidal subfields (rp = 0.7, p = 0.003) but not for the regions CA1 and dentate gyrus. In accordance with previous studies, no correlation of the FDG-PET to the neuronal cell density of CA1, CA3, and dentate gyrus was found. CONCLUSIONS: The interictal hippocampal FDG-PET hypometabolism in patients with temporal lobe epilepsy is correlated to the glucose-oxidation capacity of the CA3 hippocampal subfield as result of impaired oxidative metabolism.