Distribution of temperature changes and neurovascular coupling in rat brain following 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) exposure

(+/?)3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) is an abused psychostimulant that produces strong monoaminergic stimulation and whole‐body hyperthermia. MDMA‐induced thermogenesis involves activation of uncoupling proteins (UCPs), primarily a type specific to skeletal muscle (UCP‐3) and absent from the brain, although other UCP types are expressed in the brain (e.g. thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights into MDMA action, we measured spatial distributions of systemically administered MDMA‐induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), with an exogenous temperature‐sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetramethyl‐1,4,7,10‐tetraacetate (DOTMA^4?)). The MDMA‐induced temperature rise was greater in the cortex than in the subcortex (1.6 ± 0.4 °C versus 1.3 ± 0.4 °C) and occurred more rapidly (2.0 ± 0.2 °C/h versus 1.5 ± 0.2 °C/h). MDMA‐induced temperature changes and dynamics in the cortex and body were correlated, although the body temperature exceeded the cortex temperature before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in the cortex and subcortex (i.e. thalamus) to investigate possible differences of MDMA‐induced warming across brain regions. MDMA‐induced warming correlated with increases in neuronal activity and blood flow in the cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to the cortex, a biphasic relationship was seen in the subcortex (i.e. thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature above 37 °C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as potential heat generation) may vary regionally, neuroprotection may require different cooling strategies. Copyright © 2015 John Wiley & Sons, Ltd.     

Dynamics of changes in blood flow, volume, and oxygenation: implications for dynamic functional magnetic resonance imaging calibration.

Changes in cerebral blood flow (CBF), volume (CBV), and oxygenation (blood-oxygenation level dependent (BOLD)) during functional activation are important for calculating changes in cerebral metabolic rate of oxygen consumption (CMRo2) from calibrated functional MRI (fMRI). An important part of this process is the CBF/CBV relationship, which is signified by a power-law parameter: gamma=ln (1+DeltaCBV/CBV)/ln (1+DeltaCBF/CBF). Because of difficulty in measuring CBF and CBV with MRI, the value of gamma is therefore assumed to be approximately 0.4 from a prior primate study under hypercapnia. For dynamic fMRI calibration, it is important to know if the value of gamma varies after stimulation onset. We measured transient relationships between DeltaCBF, DeltaCBV, and DeltaBOLD by multimodal MRI with temporal resolution of 500 ms (at 7.0 T) from the rat somatosensory cortex during forepaw stimulation, where the stimulus duration ranged from 4 to 32 secs. Changes in CBF and BOLD were measured before the administration of the contrast agent for CBV measurements in the same subjects. We observed that the relationship between DeltaCBF and DeltaCBV varied dynamically from stimulation onset for all stimulus durations. Typically after stimulation onset and at the peak or plateau of the DeltaCBF, the value of gamma ranged between 0.1 and 0.2. However, after stimulation offset, the value of gamma increased to 0.4 primarily because of rapid and slow decays in DeltaCBF and DeltaCBV, respectively. These results suggest caution in using dynamic measurements of DeltaCBF and DeltaBOLD required for calculating DeltaCMRo2 for functional stimulation, when either DeltaCBV has not been accurately measured or a fixed value of gamma during hypercapnia perturbation is used.     

A critical review of chemical lymph node clearance and staging of colon and rectal cancer at Ferguson Hospital, 1977 to 1982

A unique opportunity to evaluate the method of chemical lymph node clearance for colorectal cancer exists at Ferguson Hospital. Lymph node clearance has been used at the institution since 1977, and this retrospective analysis was undertaken to ascertain its validity there. Furthermore, the node positive group was evaluated to ascertain if the current staging system (Turnbull, 1967) is prognostically accurate for the Dukes' C group. Specifically evaluated for possible prognostic variance was the survival of those patients whose tumors demonstrated partial bowel wall penetration and only one to four positive nodes, a C1 subset, previously reported to have favorable prognosis. Eight hundred sixty-four cases of colon and rectal cancer treated surgically from 1977 to 1982 were analyzed. There was a mean of 27 lymph nodes retrieved per specimen and a mean of 4.5 positive nodes per Dukes' C specimen. There were 43 C1 and 201 C2 cases with five-year survival rates of 73 and 38 percent, respectively. The results of chemical clearance at Ferguson Hospital were found to be comparable with that of other centers using chemical clearance and superior to hand dissection. The C1 subset clearly is noted to have prognostic advantage and should occupy a separate designation in any staging system.Read at the meeting of the American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.Presented at Gramec Research Day, Grand Rapids, Michigan, May 10, 1988.