Cold but not sympathomimetics activates human brown adipose tissue in vivo.

As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by (18)F-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects.

Demographics and baseline disease characteristics of Black and Hispanic patients with multiple sclerosis in the open-label, single-arm, multicenter, phase IV CHIMES trial.

BACKGROUND: Black/African American patients with multiple sclerosis (BpwMS) and Hispanic/Latino patients with multiple sclerosis (HpwMS), who historically have been underrepresented in multiple sclerosis (MS) clinical trials, exhibit greater disease severity and more rapid disease progression than White patients with MS (WpwMS). The lack of diversity and inclusion in clinical trials, which may be due to barriers at the system, patient and study levels, impacts the ability to effectively assess risks, benefits and treatment responses in a generalized patient population. METHODS: CHIMES (Characterization of Ocrelizumab in Minorities With Multiple Sclerosis), an open-label, single-arm, multicenter, phase IV study of self-identified BpwMS and HpwMS aged 18-65 years with relapsing MS and an Expanded Disability Status Score (EDSS) of ≤5.5, was developed in collaboration with patients with MS, national advocacy groups and clinical researchers. Patients were enrolled at study centers across the US, including Puerto Rico, and 1 site in Kenya. RESULTS: A total of 182 patients enrolled in CHIMES: 113 (62.1%) were BpwMS, and 69 (37.9%) were HpwMS; the mean (SD) baseline EDSS score was 2.4 (1.4), and 62.6% of patients were treatment naive. Using the pooled non-BpwMS/HpwMS group in the OPERA ocrelizumab trials as a reference population, patients enrolled in CHIMES were younger, had a higher mean body mass and had a greater T2 lesion volume but similar T2 lesion number on MRI. CONCLUSION: BpwMS and HpwMS have been consistently underrepresented in clinical trials, limiting the understanding of disease biology and response to treatment in this population. Data from the CHIMES study revealed differences in demographics and some baseline disease characteristics and disease burden between BpwMS and HpwMS vs WpwMS. These differences could have an impact when assessing clinical outcomes in BpwMS and HpwMS. GOV IDENTIFIER: NCT04377555.

Respiratory gating enhances imaging of pulmonary nodules and measurement of tracer uptake in FDG PET/CT.

OBJECTIVE: The aim of this study was to evaluate prospectively the effects of respiratory gating during FDG PET/CT on the determination of lesion size and the measurement of tracer uptake in patients with pulmonary nodules in a clinical setting. SUBJECTS AND METHODS: Eighteen patients with known pulmonary nodules (nine women, nine men; mean age, 61.4 years) underwent conventional FDG PET/CT and respiratory-gated PET acquisitions during their scheduled staging examinations. Maximum, minimum, and average standardized uptake values (SUVs) and lesion size and volume were determined with and without respiratory gating. The results were then compared using the two-tailed Student's t test and the nonparametric Wilcoxon's test to assess the effects of respiratory gating on PET acquisitions. RESULTS: Respiratory gating reduced the measured area of lung lesions by 15.5%, the axial dimension by 10.3%, and the volume by 44.5% (p = 0.014, p = 0.007, and p = 0.025, respectively). The lesion volumes in gated studies were closer to those assessed by standard CT (difference decreased by 126.6%, p = 0.025). Respiratory gating increased the measured maximum SUV by 22.4% and average SUV by 13.3% (p < 0.001 and p = 0.002). CONCLUSION: Our findings suggest that the use of PET respiratory gating in PET/CT results in lesion volumes closer to those assessed by CT and improved measurements of tracer uptake for lesions in the lungs.

Prone SPECT myocardial perfusion imaging is associated with less cardiac drift during the acquisition duration than imaging in the supine position.

BACKGROUND AND AIM: Cardiac cranial drift, a slow vertical upward displacement seen during the acquisition of myocardial single photon emission tomography (SPECT), is a source of image artefacts that may lead to erroneous interpretation. Changes in breathing pattern and depth throughout image acquisition are believed to cause cardiac cranial drift. As the physiology of respiration probably differs with postural changes, we hypothesized that cardiac drift may be different for supine vs. prone acquisitions. Our aim was to assess the magnitude of cardiac displacement for prone and supine SPECT acquisitions in patients undergoing stress myocardial perfusion imaging. METHODS: We enrolled prospectively 15 subjects undergoing exercise myocardial perfusion imaging. Subjects had post-stress images acquired in both the prone and supine positions. Motion was assessed in the horizontal (x) and vertical (y) axes for both camera heads at all 64 projections at which images were obtained. Pixel displacement (number of pixels from the baseline of zero) in either the cranial/caudal or left/right direction was quantified using the automated camera motion correction algorithm. RESULTS: Supine imaging was associated with more cranial drift than prone imaging (1.20+/-0.40 pixels vs. 0.92+/-0.24 pixels, P<0.05). There was no significant difference in cardiac displacement in the horizontal axis (1.03+/-0.5 pixels vs. 1.12+/-0.22 pixels, P=NS). CONCLUSIONS: Prone imaging is associated with less cardiac cranial drift than imaging in the supine position, suggesting that the former is associated with a more constant and reliable diaphragmatic breathing pattern. Acquisitions in the prone position may thus be associated with fewer motion artefacts than supine acquisitions for cardiac SPECT imaging.

Activation of human brown adipose tissue by a ß3-adrenergic receptor agonist.

Increasing energy expenditure through activation of endogenous brown adipose tissue (BAT) is a potential approach to treat obesity and diabetes. The class of ß3-adrenergic receptor (AR) agonists stimulates rodent BAT, but this activity has never been demonstrated in humans. Here we determined the ability of 200 mg oral mirabegron (Myrbetriq, Astellas Pharma, Inc.), a ß3-AR agonist currently approved to treat overactive bladder, to stimulate BAT as compared to placebo. Mirabegron led to higher BAT metabolic activity as measured via (18)F-fluorodeoxyglucose ((18)F-FDG) using positron emission tomography (PET) combined with computed tomography (CT) in all twelve healthy male subjects (p = 0.001), and it increased resting metabolic rate (RMR) by 203 ± 40 kcal/day (+13%; p = 0.001). BAT metabolic activity was also a significant predictor of the changes in RMR (p = 0.006). Therefore, a ß3-AR agonist can stimulate human BAT thermogenesis and may be a promising treatment for metabolic disease.

Sub-millimeter technetium-99m calibration sources.

PURPOSE: Small animal radioscintigraphic imaging systems aim to achieve sub-millimeter resolution. At the present time, sub-millimeter calibration sources that can be placed at will within an imaged volume are not readily available. We have developed a method for producing technetium-99m (Tc-99m) sources in less than 15 minutes with readily available reagents. PROCEDURES: Tc-99m pertechnetate [TcO(4)](-) was incubated with 45 microm to 106 microm diameter spherical anion exchange beads, washed, and mounted as desired for instrument calibration. RESULTS: The procedure yields spherical sources having between 6.8 microCi to 11.1 microCi of Tc-99m per source. This work shows that dual imaging of these sources using white light and radioscintigraphy permits measurement of system performance with high precision. CONCLUSION: Easily prepared, sub-millimeter Tc-99m spherical calibration sources are described, and it is demonstrated that such sources are useful for measuring the resolution and sensitivity of radioscintigraphic systems, such as those designed for small animal imaging.

The role of PET and PET/CT in managing the care of lymphoma patients.

The clinical use of PET and PET/CT aids physicians and patients in developing lymphoma prognoses, specifically for Hodgkin disease and aggressive types of non-Hodgkin lymphoma. PET and PET/CT are used to initially stage lymphoma, restage disease, and check for remission or recurrence of malignant tissue after treatment. PET/CT is more sensitive and specific than CT alone and has better accuracy concerning lymphoma relapse and remission. In conjunction with other tests, such as blood laboratory work and biopsy, PET and PET/CT allow the lymphoma to be staged appropriately and treated correctly. Results from PET and PET/CT contribute to the formation of a specialized treatment plan that leads to the best possible care for each individual patient. PET and PET/CT positively affect the management of patients with lymphoma.

Evaluation of conventional subciliary incision used in blepharoplasty: preoperative and postoperative videography and electromyography findings.

BACKGROUND: The purpose of this study was to evaluate the innervation and function of the orbicularis oculi area clinically, with video imaging, and electrically, with electromyography, before and after lower-eyelid blepharoplasty using a conventional subciliary incision. METHODS: Nine patients (18 eyes) were studied before and 4 to 12 weeks after lower-eyelid blepharoplasty. Video imaging documented clinical changes in involuntary (blink) and voluntary (squeeze and squint) eyelid function as well as resting lid position and tone. Electromyography was performed using concentric needle electrodes (25 mm in length, 0.03 mm in diameter) placed in the lateral and medial subciliary orbicularis oculi. A total of 36 sites in nine patients (four sites per patient) were studied. Acute denervation was identified by the presence of fasciculation; fibrillation potentials; insertional activity; sharp waves; and grade based on standard electromyography techniques. All patients underwent lower-eyelid blepharoplasty with a subciliary incision, skin-muscle flap and canthal anchoring with canthopexy or cantholysis, and canthoplasty. RESULTS: Video imaging of the lower eyelid before and after blepharoplasty showed evidence of eyelid malposition or abnormal voluntary or involuntary orbicularis oculi muscle function. There was no evidence of acute denervation in 34 of 36 sites (94 percent). Two patients had abnormal fasciculation in the left lateral position on two of 36 sites (6 percent). Thirty-three weeks postoperatively, one patient was retested and a normal electromyography result was obtained. CONCLUSIONS: This study demonstrated that lower-lid malposition or abnormal function after lower-lid blepharoplasty cannot be explained by denervation of the zygomatic branch of the facial nerve. Any acute or residual denervation seen in the subciliary orbicularis is not clinically significant. The importance of lower-lid support and canthal anchoring cannot be emphasized enough in preventing lower-lid malposition. Blepharoplasty is a challenging procedure that requires careful preoperative planning, intraoperative reassessment, and meticulous surgical technique to optimize facial rejuvenation and patient safety.