A single CT for attenuation correction of both rest and stress SPECT myocardial perfusion imaging: a retrospective feasibility study.

PURPOSE: In the effort to reduce radiation exposure to patients undergoing myocardial perfusion imaging (MPI) with SPECT/CT, we evaluate the feasibility of a single CT for attenuation correction (AC) of single-day rest (R)/stress (S) perfusion. METHODS: Processing of 20 single isotope and 20 dual isotope MPI with perfusion defects were retrospectively repeated in three steps: (1) the standard method using a concurrent R-CT for AC of R-SPECT and S-CT for S-SPECT; (2) the standard method repeated; and (3) with the R-CT used for AC of S-SPECT, and the S-CT used for AC of R-SPECT. Intra-Class Correlation Coefficients (ICC) and Choen's kappa were used to measure intra-operator variability in sum scoring. RESULTS: The highest level of intra-operator reliability was seen with the reproduction of the sum rest score (SRS) and sum stress score (SSS) (ICC > 95%). ICCs were > 85% for SRS and SSS when alternate CTs were used for AC, but when sum difference scores were calculated, ICC values were much lower (~22% to 27%), which may imply that neither CT substitution resulted in a reproducible difference score. Similar results were seen when evaluating dichotomous outcomes (sum scores difference of ≥ 4) when comparing different processing techniques (kappas ~0.32 to 0.43). CONCLUSIONS: When a single CT is used for AC of both rest and stress SPECT, there is disproportionately high variability in sum scoring that is independent of user error. This information can be used to direct further investigation in radiation reduction for common imaging exams in nuclear medicine.

Perfusion network shift during seizures in medial temporal lobe epilepsy.

BACKGROUND: Medial temporal lobe epilepsy (MTLE) is associated with limbic atrophy involving the hippocampus, peri-hippocampal and extra-temporal structures. While MTLE is related to static structural limbic compromise, it is unknown whether the limbic system undergoes dynamic regional perfusion network alterations during seizures. In this study, we aimed to investigate state specific (i.e. ictal versus interictal) perfusional limbic networks in patients with MTLE. METHODS: We studied clinical information and single photon emission computed tomography (SPECT) images obtained with intravenous infusion of the radioactive tracer Technetium- Tc 99 m Hexamethylpropyleneamine Oxime (Tc-99 m HMPAO) during ictal and interictal state confirmed by video-electroencephalography (VEEG) in 20 patients with unilateral MTLE (12 left and 8 right MTLE). Pair-wise voxel-based analyses were used to define global changes in tracer between states. Regional tracer uptake was calculated and state specific adjacency matrices were constructed based on regional correlation of uptake across subjects. Graph theoretical measures were applied to investigate global and regional state specific network reconfigurations. RESULTS: A significant increase in tracer uptake was observed during the ictal state in the medial temporal region, cerebellum, thalamus, insula and putamen. From network analyses, we observed a relative decreased correlation between the epileptogenic temporal region and remaining cortex during the interictal state, followed by a surge of cross-correlated perfusion in epileptogenic temporal-limbic structures during a seizure, corresponding to local network integration. CONCLUSIONS: These results suggest that MTLE is associated with a state specific perfusion and possibly functional organization consisting of a surge of limbic cross-correlated tracer uptake during a seizure, with a relative disconnection of the epileptogenic temporal lobe in the interictal period. This pattern of state specific shift in metabolic networks in MTLE may improve the understanding of epileptogenesis and neuropsychological impairments associated with MTLE.

Brain uptake of Tc99m-HMPAO correlates with clinical response to the novel redox modulating agent EPI-743 in patients with mitochondrial disease.

While decreased ATP production and redox imbalance are central to mitochondrial disease pathogenesis, efforts to develop effective treatments have been hampered by the lack of imaging markers of oxidative stress. In this study we wished to determine if Tc99m-HMPAO, a SPECT imaging marker of cerebral blood flow and glutathione/protein thiol content, could be used to monitor the effect(s) of EPI-743, an oral redox modulating, para-benzoquinone based therapeutic for mitochondrial disease. We hypothesized that treatment changes in HMPAO uptake would be inversely proportional to changes in oxidative stress within the brain and directly correlate to clinical response to EPI-743 therapy. Twenty-two patients with mitochondrial disease were treated with EPI-743. Each underwent baseline and 3-month Tc99m-HMPAO SPECT scanning along with clinical/neurologic evaluations. Diseases treated were: Leigh syndrome (n=7), polymerase γ deficiency (n=5), MELAS (n=5), Friedreich ataxia (n=2), Kearns-Sayre syndrome, Pearson syndrome, and mtDNA depletion syndrome. Neuro-anatomic uptake analyses of HMPAO were performed with NeuroGam™ (Segami Corp.) statistical software and clinical response was assessed by the Newcastle Paediatric Mitochondrial Disease Scale or Newcastle Mitochondrial Disease Adult Scale depending on patient age. For all 22 patients there was a significant linear correlation between the change in cerebellar uptake of HMPAO and the improvement in Newcastle score (r=0.623, **p=0.00161). The MELAS subgroup showed a significant relationship of whole brain uptake (n=5, r=0.917, *p=0.028) to improvement in Newcastle score. We conclude that Tc99m-HMPAO SPECT scanning has promise as a general marker of the oxidative state of the brain and its response to redox modulating therapies. Further studies will be needed to confirm these findings in a more homogenous study population.

Initial experience in the treatment of inherited mitochondrial disease with EPI-743.

Inherited mitochondrial respiratory chain disorders are progressive, life-threatening conditions for which there are limited supportive treatment options and no approved drugs. Because of this unmet medical need, as well as the implication of mitochondrial dysfunction as a contributor to more common age-related and neurodegenerative disorders, mitochondrial diseases represent an important therapeutic target. Thirteen children and one adult with genetically-confirmed mitochondrial disease (polymerase γ deficiency, n=4; Leigh syndrome, n=4; MELAS, n=3; mtDNA deletion syndrome, n=2; Friedreich ataxia, n=1) at risk for progressing to end-of-life care within 90 days were treated with EPI-743, a novel para-benzoquinone therapeutic, in a subject controlled, open-label study. Serial measures of safety and efficacy were obtained that included biochemical, neurological, quality-of-life, and brain redox assessments using technetium-99m-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) radionuclide imaging. Twelve patients treated with EPI-743 have survived; one polymerase γ deficiency patient died after developing pneumonia and one patient with Surf-1 deficiency died after completion of the protocol. Of the 12 survivors, 11 demonstrated clinical improvement, with 3 showing partial relapse, and 10 of the survivors also had an improvement in quality-of-life scores at the end of the 13-week emergency treatment protocol. HMPAO SPECT scans correlated with clinical response; increased regional and whole brain HMPAO uptake was noted in the clinical responders and the one subject who did not respond clinically had decreased regional and whole brain HMPAO uptake. EPI-743 has modified disease progression in >90% of patients in this open-label study as assessed by clinical, quality-of-life, and non-invasive brain imaging parameters. Data obtained herein suggest that EPI-743 may represent a new drug for the treatment of inherited mitochondrial respiratory chain disorders. Prospective controlled trials will be undertaken to substantiate these initial promising observations. Furthermore, HMPAO SPECT imaging may be a valuable tool for the detection of central nervous system redox defects and for monitoring response to treatments directed at modulating abnormal redox.

Diagnostic performance of In-111 capromab pendetide SPECT/CT in localized and metastatic prostate cancer.

PURPOSE: To determine the diagnostic performance of In-111 capromab pendetide single photon emission computed tomography/computed tomography (SPECT/CT), in the prostate gland, seminal vesicles, and lymph nodes via correlation to a gold standard of histopathology. MATERIALS AND METHODS: In this study, we retrospectively reviewed all In-111 capromab pendetide SPECT/CT acquired at our institution for dedicated histopathology within a 4-month period. Statistical measures of performance were calculated in terms of glandular, seminal vesicle, and lymph node activity. The accuracies of glandular and seminal vesicle activity were then correlated to the indices of risk, including the stage, Gleason score, and prostate-specific antigen level, as well as the treatment history. RESULTS: Of the 200 scans meeting the criteria of our study, 197 had prostate gland histopathology, 94 had bilateral seminal vesicle histopathology, and 5 had a total of 43 resected lymph nodes for comparison. The overall accuracies of the scan results were determined to be 77.7% (area under the receiver operating characteristic curve [AUC] = 0.539) for the gland, 67.0% (AUC = 0.510) for the seminal vesicles, and 93.0% (AUC = 0.787) for lymph nodes. For glandular activity alone, scan accuracy was found to significantly improve with increasing Gleason score (P < 0.0001), and in a setting prior to treatment (P = 0.0005). No statistically significant differences were found between different scan groups with regards to seminal vesicle activity. CONCLUSIONS: The results of this study provide substantiating evidence In-111 capromab pendetide can be used to accurately diagnose lymph node metastases from primary cancers of the prostate; however, they also suggest the test may have limited utility in diagnosing tumors within the prostate gland and seminal vesicles.

Autonomic dysfunction and gastroparesis in cirrhosis.

BACKGROUND: Patients with cirrhosis of the liver frequently present with many gastrointestinal complaints that are most likely due to abnormal gastrointestinal motility. The cause of these motility disorders in cirrhotics is unknown, however, underlying autonomic dysfunction may play a role. OBJECTIVE: To determine the association between autonomic dysfunction and delayed gastric emptying in cirrhotic patients. METHODS: We prospectively studied 20 patients with cirrhosis of the liver and postprandial abdominal pain, nausea, and vomiting and 10 asymptomatic patients with Hepatitis C (HCV) and no evidence of cirrhosis. All patients underwent 5 standardized cardiovascular tests to assess autonomic function. Each test was scored on a continuum from 0 (normal) to 5 (severe disease), thus producing a composite score of 0 to 5 for each subject. A composite score of greater than 1.5 was considered abnormal, with 5 representing severe autonomic involvement. A solid phase gastric emptying study was performed in each patient and a gastric retention of greater than 50% at 100 minutes was considered abnormal. RESULTS: The mean percent retention at 100 minutes was 70.7% in the cirrhotic group vs. 26.1% (P < 0.001) in the patients with HCV and no evidence of cirrhosis (controls). The composite autonomic score for the cirrhotic group was 3.4 vs. 1.2 (P < 0.001) in the controls. CONCLUSIONS: Our results suggest that gastroparesis is common in patients with cirrhosis of the liver, and may account for gastrointestinal symptoms of postprandial abdominal pain, nausea, and vomiting. The presence of autonomic dysfunction correlates positively with underlying motility disorders, such as delayed gastric emptying.