Madhavi Tripathi

Comparative evaluation of F-18 FDOPA, F-18 FDG, and F-18 FLT-PET/CT for metabolic imaging of low grade gliomas.

Introduction: We undertook this prospective study to compare amino acid metabolism, glucose metabolism, and proliferation in primary and recurrent low grade gliomas using positron emission tomography (PET)/computed tomography with F-18 FDOPA, F-18 FDG, and F-18 FLT. Methods: Fifteen patients with newly diagnosed or previously treated low grade gliomas (WHO grade I or II) were subjected to F-18-FDOPA, F-18 FDG, and F-18 FLT PET/computed tomography studies on consecutive days. This included 2 patients in remission as control subjects. Uptake of all the 3 tracers were analyzed visually and quantified using standardized uptake values and tumor to normal (T/N) ratios. The accuracy of all the 3 PET tracers in the detection of newly diagnosed and recurrent low grade gliomas was compared. Results: F-18 FDOPA was positive in all cases of primary and recurrent low grade gliomas and negative in the patients in remission. Tumor was visualized on F-18 FDG in 7 of 13 cases, F-18-FLT was positive in 4 of 13 cases. Average tumor standardized uptake values max for F-18 FDOPA (5.75 ± 4.9) and F-18 FLT (1.8 ± 0.91) was lower than that of F-18 FDG (8.5 ± 4.4). T/N ratios for F-18-FDOPA (2.3 ± 0.51) and F-18 FLT (1.8 ± 0.91) were higher than F-18 FDG (1.03 ± 0.64) providing good image contrast for tumor detection in positive cases. Conclusion: F-18 FDOPA scan is superior to both F-18 FLT and F-18 FDG for visualization of primary and recurrent low grade gliomas. F-18-FLT should not be considered for evaluation of recurrent low grade gliomas.

Comparison of F-18 FDG and C-11 methionine PET/CT for the evaluation of recurrent primary brain tumors.

Purpose of Study: With the availability of multiple positron emission tomography (PET) tracers for neurooncology, there is a need to define the appropriate tracer in a given clinical setting, and it is in this regard that we undertook this study to directly compare F-18 flurodeoxyglucose (FDG) PET and C-11 methionine (MET) PET for the evaluation of recurrence in primary brain tumors. Patients and Methods: Thirty-seven patients with a history of treated primary brain tumors referred for evaluation of recurrent disease were initially included in the study. Two patients had to be excluded because of insufficient follow-up. There were 23 males and 12 females, mean age: 33.7 ± 16.4 years; range: 5 to 65 years. All patients underwent the MET and FDG study on the same day. Visual image interpretation was performed independently by 2 PET physicians for each tracer using the plain PET and fused PET/CT images; the FDG images were evaluated first. Images were analyzed semiquantitatively using tumor to normal contralateral cortex ratios (T/N). Each patient was followed up for a minimum of 18 months. Imaging results were compared with histopathology on tumor excision or biopsy in 14 patients and with clinical follow-up and MRI/MRS at the end of 18 months in 21 patients. Results: The final diagnosis was tumor recurrence in 24 patients and no recurrence/stable disease in 11 patients. On FDG, findings in 15/35 (42%) were suggestive of recurrent tumors. On MET, findings in 24/34 (70.5%) cases were suggestive of recurrent tumors. Spatially separated secondary lesions including intraventricular deposits were clearly delineated in 5 cases, 3 were glioblastoma multiforme (GBM) and 2 were anaplastic astrocytomas. One of the secondary lesions was missed on FDG PET. Using a cutoff for T/N ratio on FDG of >0.75 to differentiate recurrence from no recurrence, sensitivity of FDG was 81.2% (confidence interval [CI] = 54.4%–96%), whereas specificity was 88.9% (CI = 51.8%–99.7%). Area under the curve was 0.819 (CI = 0.615–0.943), P = 0.0003. Using a cutoff for T/N ratio of >1.9 to differentiate recurrence from no recurrence, sensitivity of MET was 94.7% (CI = 74.0%–99.9%), whereas specificity was 88.89% (CI = 51.8%–99.7%). Area under the curve was 0.942 (CI = 0.785–0.995), P < 0.0001. Interobserver agreement, &kgr; coefficient, for MET was 0.93, suggesting good interobserver agreement, whereas for FDG, it was fair (0.23). Conclusions: MET should be the radiotracer of choice in the evaluation of recurrence of primary brain tumors because the sensitivity for detection and delineation of the possible recurrent tumor, as well as secondary deposits, is higher with MET. MET-PET is an easier technique to interpret, irrespective of the glioma grade, with less interobserver variability and straightforward localization of tumorous accumulation.

Metastatic poorly differentiated prostatic carcinoma with neuroendocrine differentiation: negative on 68Ga-PSMA PET/CT.

Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68(HBED-CC)], abbreviated as Ga-PSMA, is a novel radiotracer undergoing evaluation for PET/CT imaging of prostate carcinoma. Its major advantage is the sensitive detection of lesions even at low prostate-specific antigen level and high target-to-background ratios obtained in metastatic lesions, which is better than that obtained with F-fluoromethylcholine. We present the case of a 28-year-old man with poorly differentiated prostate carcinoma with neuroendocrine differentiation, whose lesions did not show significant Ga-PSMA localization. As literature on utility of Ga-PSMA PET/CT for imaging prostate carcinoma grows, it is important to be aware of potential false negatives that could influence study results.

Surgery for Drug-Resistant Epilepsy in Children

BACKGROUND Neurosurgical treatment may improve seizures in children and adolescents with drug‐resistant epilepsy, but additional data are needed from randomized trials. METHODS In this single‐center trial, we randomly assigned 116 patients who were 18 years of age or younger with drug‐resistant epilepsy to undergo brain surgery appropriate to the underlying cause of epilepsy along with appropriate medical therapy (surgery group, 57 patients) or to receive medical therapy alone (medical‐therapy group, 59 patients). The patients in the medical‐therapy group were assigned to a waiting list for surgery. The primary outcome was freedom from seizures at 12 months. Secondary outcomes were the score on the Hague Seizure Severity scale, the Binet–Kamat intelligence quotient, the social quotient on the Vineland Social Maturity Scale, and scores on the Child Behavior Checklist and the Pediatric Quality of Life Inventory. RESULTS At 12 months, freedom from seizures occurred in 44 patients (77%) in the surgery group and in 4 (7%) in the medical‐therapy group (P<0.001). Between‐group differences in the change from baseline to 12 months significantly favored surgery with respect to the score on the Hague Seizure Severity scale (difference, 19.4; 95% confidence interval [CI], 15.8 to 23.1; P<0.001), on the Child Behavior Checklist (difference, 13.1; 95% CI, 10.7 to 15.6; P<0.001), on the Pediatric Quality of Life Inventory (difference, 21.9; 95% CI, 16.4 to 27.6; P<0.001), and on the Vineland Social Maturity Scale (difference, 4.7; 95% CI, 0.4 to 9.1; P=0.03), but not on the Binet–Kamat intelligence quotient (difference, 2.5; 95% CI, ‐0.1 to 5.1; P=0.06). Serious adverse events occurred in 19 patients (33%) in the surgery group, including hemiparesis in 15 (26%). CONCLUSIONS In this single‐center trial, children and adolescents with drug‐resistant epilepsy who had undergone epilepsy surgery had a significantly higher rate of freedom from seizures and better scores with respect to behavior and quality of life than did those who continued medical therapy alone at 12 months. Surgery resulted in anticipated neurologic deficits related to the region of brain resection. (Funded by the Indian Council of Medical Research and others; Clinical Trial Registry–India number, CTRI/2010/091/000525.)

Samarium-153 ethylenediamine tetramethylene phosphonate therapy for bone pain palliation in skeletal metastases

BACKGROUND Systemic therapy with radionuclides may be used for the treatment of patients with painful skeletal metastases owing to its efficacy, low cost and low toxicity. Imported radionuclides for pain palliation, like Strontium-89 are expensive; particularly for developing countries. In the Indian scenario, Samarium-153 (Sm-153) is produced in our own reactors and as a result, it is readily available and economical. AIM We undertook this study to determine the efficacy and toxicity of single-dose Sm-153 ethylenediamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases. MATERIALS AND METHODS Eightysix patients with painful skeletal metastases from various primaries, were treated with Sm-153 EDTMP at a dose of 37 MBq/kg. The effects were evaluated according to change in visual analogue pain score, analgesic consumption, Karnofsky performance score, mobility score and blood count tests, conducted regularly for 16 weeks. STATISTICS Repeated measures analysis. RESULTS The overall response rates were 73%, while complete response was seen in 12.4%. Reduction in analgesic consumption with improvement in Karnofsky performance score and mobility score, was seen in all responders. Response rates were 80.3 and 80.5% in breast and prostate cancer, respectively. One case, each of Wilms tumor, ovarian cancer, germ cell tumor testis, multiple myeloma, primitive neuroectodermal tumor and oesophageal cancer, did not respond to therapy. No serious side-effects were noted, except for fall in white blood cell, platelet and haemoglobin counts, which gradually returned to normal levels by six-eight weeks. CONCLUSION Sm-153 EDTMP provided effective palliation in 73% patients with painful bone metastases: the major toxicity was temporary myelosuppression.

Automated Differential Diagnosis of Early Parkinsonism using Metabolic Brain Networks: A Validation Study

The differentiation of idiopathic Parkinson disease (IPD) from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the most common atypical parkinsonian look-alike syndromes (APS), can be clinically challenging. In these disorders, diagnostic inaccuracy is more frequent early in the clinical course when signs and symptoms are mild. Diagnostic inaccuracy may be particularly relevant in trials of potential disease-modifying agents, which typically involve participants with early clinical manifestations. In an initial study, we developed a probabilistic algorithm to classify subjects with clinical parkinsonism but uncertain diagnosis based on the expression of metabolic covariance patterns for IPD, MSA, and PSP. Classifications based on this algorithm agreed closely with final clinical diagnosis. Nonetheless, blinded prospective validation is required before routine use of the algorithm can be considered. Methods: We used metabolic imaging to study an independent cohort of 129 parkinsonian subjects with uncertain diagnosis; 77 (60%) had symptoms for 2 y or less at the time of imaging. After imaging, subjects were followed by blinded movement disorders specialists for an average of 2.2 y before final diagnosis was made. When the algorithm was applied to the individual scan data, the probabilities of IPD, MSA, and PSP were computed and used to classify each of the subjects. The resulting image-based classifications were then compared with the final clinical diagnosis. Results: IPD subjects were distinguished from APS with 94% specificity and 96% positive predictive value (PPV) using the original 2-level logistic classification algorithm. The algorithm achieved 90% specificity and 85% PPV for MSA and 94% specificity and 94% PPV for PSP. The diagnostic accuracy was similarly high (specificity and PPV > 90%) for parkinsonian subjects with short symptom duration. In addition, 25 subjects were classified as level I indeterminate parkinsonism and 4 more subjects as level II indeterminate APS. Conclusion: Automated pattern-based image classification can improve the diagnostic accuracy in patients with parkinsonism, even at early disease stages.

Prospective evaluation of CECT and 18F-FDG-PET/CT in detection of hepatic metastases.

ObjectivesThe purpose of this study was to evaluate the performance of 18F-fluorodeoxy-D-glucose (FDG)-PET/computed tomography (CT) and contrast-enhanced CT (CECT) in the detection and characterization of hepatic metastases. MethodsForty-five patients harboring an extrahepatic primary malignancy, with suspected hepatic metastases on clinical or ultrasonographic examination were enroled prospectively. Each patient underwent contrast-enhanced abdominal CT and 18F-FDG-PET/CT within 72 h of each other, reported by an experienced radiologist and nuclear medicine specialist, respectively in a blinded manner. CECT and PET-CT findings were compared and analyzed. Final diagnosis was based on histology and/or follow-up (ranging from 6 to 12 months). ResultsThe sensitivity and specificity of CECT in the detection of hepatic metastases was 87.9 and 16.7%, respectively, whereas that of PET/CT was 97 and 75%, respectively. This study showed the superiority of PET/CT over CECT in the detection of hepatic metastases, irrespective of the primary site. This was especially owing to the latters inability to reliably distinguish small (less than 15 mm) lesions as benign or malignant. ConclusionMany studies have been conducted on the impact of FDG-PET/CT in the evaluation of hepatic metastases, especially from colorectal primary. Very few prospective studies, however, have been conducted on its role in evaluation of hepatic metastases from nongastrointestinal primaries. Despite its superior performance, it cannot replace CECT for this purpose, owing to the low but definite risk of false positivity based on PET-CT findings alone. Inclusion of CECT in PET/CT protocols may enable us to achieve a higher diagnostic accuracy. This suggests the need for a large prospective study with serial evaluations and pathological correlation.

Surgical outcome of cortical dysplasias presenting with chronic intractable epilepsy: a 10-year experience.

BACKGROUND There has been sparse description of cortical dysplasias (CDs) causing intractable epilepsy from India. AIM Clinical retrospective study of CDs causing intractable epilepsy that underwent surgery. MATERIALS AND METHODS Fifty-seven cases of CDs reviewed (1995 till July 2006) are presented. All patients had intractable epilepsy, and underwent a complete epilepsy surgery workup (inter ictal electroencephalography (EEG), video EEG, MRI as per epilepsy protocol, SPECT {interictal, ictal with subtraction and co-registration when required}, and PET when necessary). Surgical treatment included a wide exposure of the pathology with a detailed electrocorticography under optimal anesthetic conditions. Mapping of the sensori-motor area was performed where indicated. Procedures included resection either alone or combined with multiple subpial transactions when extending into the eloquent areas. RESULTS Our study had 28 (49.12%) cases of isolated focal CDs, and 29 (50.67%) with dual pathology. Average age at the time of onset of seizures in our series was 7.04 years (three months to 24 years), and average age at the time of surgery was 10.97 years (eight months to 45 years). Among coexistent pathologies, one had associated MTS, 16 had coexistent gangliogliomas and 12 (dysembryonic neuroepithelial tumor) DNTs. At an average follow-up of 3.035 years (range 5-10 years), three patients were lost to follow-up. Fifty-one per cent (29/57) patients had a good outcome (Engel Grade I) and 26%(15/57) had a Grade II outcome. CONCLUSION Cortical dysplasias have a good outcome if evaluated and managed with concordant electrical and imaging modalities.

Metastatic follicular carcinoma of the thyroid with tumor thrombus in the superior vena cava and right brachiocephalic and internal jugular veins: FDG-PET/CT findings.

Abstract:A 48-year-old woman who had undergone subtotal thyroidectomy with right modified neck dissection underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for assessing the extent of disease postoperatively (restaging). Biopsy was reported as follicular carcinoma thyroid. A

Detection of brain metastasis with 68Ga-labeled PSMA ligand PET/CT: a novel radiotracer for imaging of prostate carcinoma.

Brain metastasis in prostate cancer is rare and not expected at initial presentation especially when the patient is asymptomatic for the same. A 45-year-old male patient undergoing initial evaluation for newly diagnosed prostatic adenocarcinoma was referred to our department for 99mTc-MDP bone scintigraphy. As part of the study protocol, he also underwent Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68(HBED-CC)] (68Ga-PSMA) PET/CT, which revealed tracer accumulation in brain lesions, apart from localization in the primary, lymph node, and bone metastases. A subsequent MR evaluation confirmed brain metastases.