A pilot dose-finding study of Terazosin in humans.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder where progressive neuron loss is driven by impaired brain bioenergetics, particularly mitochondrial dysfunction and disrupted cellular respiration. Terazosin (TZ), an α-1 adrenergic receptor antagonist with a known efficacy in treating benign prostatic hypertrophy and hypertension, has shown potential in addressing energy metabolism deficits associated with PD due to its action on phosphoglycerate kinase 1 (PGK1). This study aimed to investigate the safety, tolerability, bioenergetic target engagement, and optimal dose of TZ in neurologically healthy subjects.

Differences in Inhibitory Control and Resting Brain Metabolism between Older Chronic Users of Tetrahydrocannabinol (THC) or Cannabidiol (CBD)-A Pilot Study.

Δ9-Tetrahydrocannabinol is the main psychoactive component of cannabis and cannabidiol is purportedly responsible for many of the medicinal benefits. The effects of Δ9-tetrahydrocannabinol and cannabidiol in younger populations have been well studied; however, motor function, cognitive function, and cerebral glucose metabolism in older adults have not been extensively researched. The purpose of this study was to assess differences in cognitive function, motor function, and cerebral glucose metabolism (assessed via [F]-fluorodeoxyglucose positron emission tomography) in older adults chronically using Δ9-tetrahydrocannabinol, cannabidiol, and non-using controls.

F-FDG-PET Imaging for Post-COVID-19 Brain and Skeletal Muscle Alterations.

Scientific evidence concerning the subacute and long-term effects of coronavirus disease 2019 (COVID-19) is on the rise. It has been established that infection by serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a systemic process that involves multiple organs. The complications and long-term consequences of COVID-19 are diverse and patients need a multidisciplinary treatment approach in the acute and post-acute stages of the disease.

Alterations in Leg Muscle Glucose Uptake and Inter-Limb Asymmetry after a Single Session of tDCS in Four People with Multiple Sclerosis.

Asymmetrical lower limb weakness is an early symptom and significant contributor to the progressive worsening of walking ability in people with multiple sclerosis (PwMS). Transcranial direct current stimulation (tDCS) may effectively increase neural drive to the more-affected lower limb and, therefore, increase symmetrical activation. Four PwMS (1 female, age range: 27-57) underwent one session each of 3 mA or SHAM tDCS over the motor cortex corresponding to their more-affected limb followed by 20 min of treadmill walking at a self-selected speed.

Radiopharmaceutical Delivery for Theranostics: Pharmacokinetics and Pharmacodynamics.

Theranostics is a new and evolving combination diagnostic and/or therapeutic approach that is demonstrating efficacy for treatment of a growing number of cancers. In this approach, a diagnostic radiopharmaceutical is used in concert with positron-emission tomography (PET) or single photon emission computed tomography (SPECT) imaging to identify whether a cancer-specific membrane protein is strongly expressed on a patient's tumors. If the molecular target is detected with sufficient specificity and uptake, a therapeutic radiopharmaceutical, nearly identical to the diagnostic radiopharmaceutical except labeled with a longer-lived alpha or beta-emitting radionuclide, is administered at a therapeutic dose level to treat the cancer.

Individual Cerebral Blood Flow Responses to Transcranial Direct Current Stimulation at Various Intensities.

Transcranial direct current stimulation (tDCS) has been shown to alter cortical excitability. However, it is increasingly accepted that tDCS has high inter- and intra-subject response variability, which currently limits broad application and has prompted some to doubt if the current can reach the brain. This study reports individual cerebral blood flow responses in people with multiple sclerosis and neurologically healthy subjects that experienced 5 min of anodal tDCS at 1 mA, 2 mA, 3 mA, and 4 mA over either the dorsolateral prefrontal cortex (DLPFC) or the primary motor cortex (M1).

Different Effects of Transcranial Direct Current Stimulation on Leg Muscle Glucose Uptake Asymmetry in Two Women with Multiple Sclerosis.

Asymmetrical lower limb strength is a significant contributor to impaired walking abilities in people with multiple sclerosis (PwMS). Transcranial direct current stimulation (tDCS) may be an effective technique to enhance cortical excitability and increase neural drive to more-affected lower limbs. A sham-controlled, randomized, cross-over design was employed.

Imaging Transcranial Direct Current Stimulation (tDCS) with Positron Emission Tomography (PET).

Transcranial direct current stimulation (tDCS) is a form of non-invasive neuromodulation that is increasingly being utilized to examine and modify several cognitive and motor functions. Although tDCS holds great potential, it is difficult to determine optimal treatment procedures to accommodate configurations, the complex shapes, and dramatic conductivity differences among various tissues. Furthermore, recent demonstrations showed that up to 75% of the tDCS current applied to rodents and human cadavers was shunted by the scalp, subcutaneous tissue, and muscle, bringing the effects of tDCS on the cortex into question.

No Immediate Effects of Transcranial Direct Current Stimulation at Various Intensities on Cerebral Blood Flow in People with Multiple Sclerosis.

Animal and transcranial magnetic stimulation motors have evoked potential studies suggesting that the currently used transcranial direct current stimulation (tDCS) intensities produce measurable physiological changes. However, the validity, mechanisms, and general efficacy of this stimulation modality are currently being scrutinized. The purpose of this pilot study was to investigate the effects of dorsolateral prefrontal cortex tDCS on cerebral blood flow.

Early Phase PIB-PET as a Surrogate for Global and Regional Cerebral Blood Flow Measures.

Background And Purpose: To explore the potential for simplified measures of [ C]PIB uptake to serve as a surrogate for cerebral blood flow (CBF) measures, thereby, providing both pathological and functional information in the same scan.

Methods: Participants (N = 24, 16 M, 8 F, 57-87 years) underwent quantitative [ O]water imaging and dynamic [ C]PIB imaging. Time-activity curves were created for each participant's regional [ C]PIB data scaled in standardized uptake values (SUVs).

Demonstration of Nucleoside Transporter Activity in the Nose-to-Brain Distribution of [F]Fluorothymidine Using PET Imaging.

To evaluate the role of nucleoside transporters in the nose-to-brain uptake of [F]fluorothymidine (FLT), an equilibrative nucleoside transporter (ENT1,2) and concentrative nucleoside transporter (CNT1-3) substrate, using PET to measure local tissue concentrations. Anesthetized Sprague-Dawley rats were administered FLT by intranasal (IN) instillation or tail-vein injection (IV). NBMPR (nitrobenzylmercaptopurine riboside), an ENT1 inhibitor, was administered either IN or intraperitoneally (IP).

Pharmacoimaging of Blood-Brain Barrier Permeable (FDG) and Impermeable (FLT) Substrates After Intranasal (IN) Administration.

To illustrate the use of imaging to quantify the transfer of materials from the nasal cavity to other anatomical compartments, specifically, transfer to the brain using the thymidine analogue, [F]fluorothymidine (FLT), and the glucose analogue, [F]fluorodeoxyglucose (FDG). Anesthetized rats were administered FLT or FDG by intranasal instillation (IN) or tail-vein injection (IV). PET/CT imaging was performed for up to 60 min.

Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism.

The brain-specific isoform of renin (Ren-b) has been proposed as a negative regulator of the brain renin-angiotensin system (RAS). We analyzed mice with a selective deletion of Ren-b which preserved expression of the classical renin (Ren-a) isoform. We reported that Ren-b mice exhibited central RAS activation and hypertension through increased expression of Ren-a, but the dipsogenic and metabolic effects in Ren-b mice are unknown.

Using [(18)F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients.

Purpose: The purpose of the present prospective clinical trial was to determine the efficacy of [(18)F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity.

Methods And Materials: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow.

Fluorine-18-Labeled Thymidine Positron Emission Tomography (FLT-PET) as an Index of Cell Proliferation after Pharmacological Ascorbate-Based Therapy.

Pharmacological ascorbate (AscH(-)) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells compared with normal cells. Positron emission tomography (PET) with the thymidine analog 3'-deoxy-3'-((18)F) fluorothymidine (FLT) enables noninvasive imaging and quantification of the proliferation fraction of tumors. We hypothesized that the rate of tumor proliferation determined by FLT-PET imaging, would be inversely proportional to tumor susceptibility to pharmacological AscH(-)-based treatments.

Preliminary Investigation of Cerebral Blood Flow and Amyloid Burden in Veterans With and Without Combat-Related Traumatic Brain Injury.

This study aimed to examine global and regional cerebral blood flow and amyloid burden in combat veterans with and without traumatic brain injury (TBI). Cerebral blood flow (in milliliters per minute per 100 mL) was measured by quantitative [(15)O]water, and amyloid burden was measured by [(11)C]PIB imaging. Mean global cerebral blood flow was significantly lower in veterans with TBI compared with non-TBI veterans.

Regulation of glucose tolerance and sympathetic activity by MC4R signaling in the lateral hypothalamus.

Melanocortin 4 receptor (MC4R) signaling mediates diverse physiological functions, including energy balance, glucose homeostasis, and autonomic activity. Although the lateral hypothalamic area (LHA) is known to express MC4Rs and to receive input from leptin-responsive arcuate proopiomelanocortin neurons, the physiological functions of MC4Rs in the LHA are incompletely understood. We report that MC4R(LHA) signaling regulates glucose tolerance and sympathetic nerve activity.

Spatial mapping of functional pelvic bone marrow using FLT PET.

The purpose of this study was to determine the ability of regions identified with bony landmarks on CT imaging to accurately represent active bone marrow when compared to FLT PET imaging. These surrogate regions could then be used to create a bone marrow sparing radiation therapy plan when FLT PET imaging is not available. Whole body (WB) FLT PET images were obtained of 18 subjects prior to chemoradiation therapy.

Frontal hypometabolism in elderly breast cancer survivors determined by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET): a pilot study.

Purpose: The term "chemobrain" is sometimes used to denote deficits in neuropsychological functioning that may occur as a result of cancer treatment. As breast cancer survivors now commonly reach late life, it is not known whether previous exposure to chemotherapy may affect long-term risk for cognitive impairment. To help address this concern, this study tested whether successfully surviving chemotherapy earlier in life was associated with later differences in brain metabolic function as an older adult compared to controls.

Repeatability of gallium-68 DOTATOC positron emission tomographic imaging in neuroendocrine tumors.

Objective: To evaluate the repeatability of gallium-68 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA)-D-Phe1-Try3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) in neuroendocrine tumors.

Methods: Five patients with neuroendocrine tumors were imaged with 68Ga-DOTATOC PET twice within 5 days. Maximum and mean standardized uptake values (SUVmax and SUVmean) and kinetic parameters (K-Patlak and K-influx) of target lesions were measured.

The biology of linguistic expression impacts neural correlates for spatial language.

Biological differences between signed and spoken languages may be most evident in the expression of spatial information. PET was used to investigate the neural substrates supporting the production of spatial language in American Sign Language as expressed by classifier constructions, in which handshape indicates object type and the location/motion of the hand iconically depicts the location/motion of a referent object. Deaf native signers performed a picture description task in which they overtly named objects or produced classifier constructions that varied in location, motion, or object type.

Emotional blunting following left basal ganglia stroke: the role of depression and fronto-limbic functional alterations.

Disorders of the basal ganglia (BG) alter perception and experience of emotions. Left hemisphere BG (LBG) stroke is also associated with depression. The interplay between depression and alterations in emotional processing following LBG stroke was examined.

Eyeblink conditioning in healthy adults: a positron emission tomography study.

Eyeblink conditioning is a paradigm commonly used to investigate the neural mechanisms underlying motor learning. It involves the paired presentation of a tone-conditioning stimulus which precedes and co-terminates with an airpuff unconditioned stimulus. Following repeated paired presentations a conditioned eyeblink develops which precedes the airpuff.

Effects of chronic marijuana use on brain activity during monetary decision-making.

Marijuana (MJ) acutely acts on cannabinoid receptors that are found in numerous brain regions, including those involved in reward processing and decision-making. However, it remains unclear how long-term, chronic MJ use alters reward-based decision-making. In the present study, using [(15)O]water PET imaging, we measured brain activity in chronic MJ users, who underwent monitored abstinence from MJ for approximately 24 h before imaging, and control participants, while they took part in the Iowa Gambling Task (IGT), a monetary decision making task that strongly relies on the ventromedial prefrontal cortex (vmPFC).

Sign language and pantomime production differentially engage frontal and parietal cortices.

We investigated the functional organization of neural systems supporting language production when the primary language articulators are also used for meaningful, but non-linguistic, expression such as pantomime. Fourteen hearing non-signers and 10 deaf native users of American Sign Language (ASL) participated in an H(2) (15)O-PET study in which they generated action pantomimes or ASL verbs in response to pictures of tools and manipulable objects. For pantomime generation, participants were instructed to "show how you would use the object.