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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.

Introduction Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). Methods A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Results Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. Conclusion FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample.

An arithmetic procedure was developed to determine the radioactivity required for an attenuation-correction transmission source for the delivery of a predetermined patient radiation dose for various patient-source configurations. The procedure determines the absorbed energy per incident photon from a chosen transmission radionuclide, based on Monte Carlo data. Results were verified using TLD and ionization chamber measurements. The method is useful in calculating the transmission source radioactivity for transmission computed tomography using a two-dimensional transmission source.

Coronary artery disease is frequently present in patients undergoing evaluation for reconstructive peripheral vascular surgery. Dobutamine-thallium imaging has been shown to be a reliable and sensitive noninvasive method for the detection of significant coronary artery disease. Eighty-seven candidates for vascular reconstruction underwent dobutamine-thallium imaging. Forty-eight patients had an abnormal dobutamine-thallium scan. Twenty-two patients had infarct only, while 26 had reversible ischemia demonstrated on dobutamine-thallium imaging. Fourteen of 26 patients with reversible ischemia underwent cardiac catheterization and 11 showed significant coronary artery disease. Seven patients underwent preoperative coronary artery bypass grafting or angioplasty. There were no postoperative myocardial events in this group. Three patients were denied surgery on the basis of unreconstructible coronary artery disease, and one patient refused further intervention. Ten patients with reversible myocardial ischemia on dobutamine-thallium imaging underwent vascular surgical reconstruction without coronary revascularization and suffered a 40% incidence of postoperative myocardial ischemic events. Five patients were denied surgery because of presumed significant coronary artery disease on the basis of the dobutamine-thallium imaging and clinical evaluation alone. Thirty-nine patients with normal dobutamine-thallium scans underwent vascular reconstructive surgery with a 5% incidence of postoperative myocardial ischemia. Dobutamine-thallium imaging is a sensitive and reliable screening method which identifies those patients with coronary artery disease who are at high risk for perioperative myocardial ischemia following peripheral vascular surgery.