There is still no practical, theoretically sound method for directly measuring cerebral mean transit time (MTT) from MRI data 1,2. We have derived a novel theory for measuring MTT suitable for perfusion MRI data and tested this theory in dogs. The theory shares the assumptions of the central volume theorem for an inert, intravascular tracer but also assumes that the system can be described by a single mean path with a single MTT for each ROI. After fitting the perfusion data for tissue and artery to a gamma variate function, it can be shown that MTT is found by solving the non-linear equation (1 - exp(- MTT / tart)) / (MTT / tart) = tart)/ ttis, where the peak in the arterial curve is at time t art, the peak in the tissue curve is at time (ttis+ ΔAT) and ΔAT is the difference in contrast arrival times between artery and tissue. Male, 15 kg, purpose-bred hounds (n = 6) were anesthetized with IV acepromazine and pentobarbital. MRI sequences were acquired on a 1.5 T Picker Edge and included single shot echo p...

Pupose: This study was done to determine whether diffusion MRI (dMRI) can detect neuroprotective and regenerative effects of fibroblasts secreting brain derived neurotrophic factor (Fb-BDNF) in the white matter (WM) of the spinal cord following injury. Materials and Methods: Unmodified fibroblasts (Fb-UM) (N=2) or Fb-BDNF (N=2) were placed in a hemisection cavity. Sacrifice was at 1 or 8 weeks. Following perfusion fixation, dMRI was performed. Apparent diffusion coefficients (ADC's) parallel and perpendicular to the long axis of the cord were obtained in the rubrospinal tract (RST) where prior research has shown that Fb-BDNF transplants provide neuroprotection and promote axonal regeneration. Results: At 1 week, Fb-UM and Fb-BDNF ADC's in WM were similar, however abnormal as compared to control. At 8 weeks, ADC's rostral to the transplant were near normal in Fb-BDNF, while remaining abnormal in Fb-UM. The anisotropy index, abnormal in Fb-UM and Fb-BDNF at 1 week, was near normal rostral in Fb-BDNF by 8 wee...

Regulation of dopamine release and synthesis is thought to occur via pre-synaptic dopamine(DA) D2 autoreceptors. Selective mapping of autoreceptors in vivo is difficult, as their function is best assessed using dynamic measures of DA release such as microdialysis. We show here that pharmacologic MRI (phMRI) may also prove useful for this purpose. First, we mapped the phMRI response to acute agonism and antagonism of D2 receptors using either quinpirole or eticlopride. These ligands lead to small change in relative cerebral blood volume (rCBV)(<10%) in stiratum (Str), nucleus accumbens (NAcc), and cingulate cortex. We then studied the response to an amphetamine (AMPH) challenge using pre- and post-treatment with eticlopride and quinpirole. Agonism of D2 receptors using quinpirole lead to a large decrease in rCBV changes induced by AMPH in Str and NAcc, but had little effect in frontal cortex (FCtx). Conversely, antagonism of D2 receptors with eticlopride lead to a large potentiation of rCBV changes induced ...

We used pharmacological MRI (phMRI) to study dopamine (DA) systems in the rat brain, by measuring changes in local brain activity after administration of amphetamine (Amp) with and without two other dopaminergic drugs. For phMRI Amp is idea as a tool, due to its well-characterised and robust response as well being an indirect DA agonist (on both D1 and D2-type of DA receptors). Thus by manipulating Amp stimulation using specific D1 and D2 antagonists, one may be able to ascertain for which components of the phMRI response the receptor types are responsible, with the ultimate goal of gaining information on the nature of the BOLD signal regarding transmitter interaction. T2-weighted fMRI (2.35T Bruker system) was used to identify the pattern and determinants of Amp-induced brain activation in drug-naïve rats (3mg/kg, i.v, n=8). Additionally we investigated the effect of pre-treating individual cohorts of rats with D1 antagonist SCH23390(0.5mg/kg, i.v, n=8) or sulpiride (50mg/kg, i.v, n=8) before acute challe...

A 3D seeded region growing technique was applied to MRI images of the spinal cord in order to separate morphological features such as gray and white matter. This technique was implemented to overcome the problems in delineating boundaries between morphologic structures using standard clinical MRI scans (T1, T2, continuous slice) of the spinal cord. Traditional images are 256 levels of gray with no clear delineation between white matter and gray matter tracts. Threshold based segmentation techniques, which are typically used for the identification of morphologic boundaries, are not adequate for this problem due to the nature of the MRI images. Small pockets of supposed white matter appear in gray matter and vice versa. The 3D seeded region growing technique takes advantage of both inter-slice and intra-slice variations in gray level to segment gray and white matter and insure that the regions are contiguous. This eliminates the pockets that would occur if a simple threshold were used. Once segmented, the da...

Stereoscopic vision enables the perception of depth. To study the brain mechanisms behind stereoscopic vision using non-invasive brain imaging (‘MRI’), scientists need to reproduce the independent views of the left and right eyes in the brain scanner using ‘dichoptic’ displays. However, high quality dichoptic displays are technically challenging and costly to implement in the MRI scanner. The novel miniature stereoscope system (‘MRI stereoscope’) is an affordable and open-source tool that displays high-quality dichoptic images inside the MRI scanner. The MRI stereoscope takes advantage of commonly used display equipment, the MRI head coil, and a display screen. To validate the MRI stereoscope, binocular disparity stimuli were presented in a 3T MRI scanner while neural activation was recorded using functional MRI in six human participants. The comparison of large binocular disparities compared to disparities close to zero evoked strong responses across dorsal and ventral extra-striate visual cortex. In cont...

Stereoscopic vision enables the perception of depth. To study the brain mechanisms behind stereoscopic vision using noninvasive brain imaging (magnetic resonance brain imaging; MRI), scientists need to reproduce the independent views of the left and right eyes in the brain scanner using “dichoptic” displays. However, high-quality dichoptic displays are technically challenging and costly to implement in the MRI scanner. The novel miniature stereoscope system (“MRI stereoscope”) is an affordable and open-source tool that displays high-quality dichoptic images inside the MRI scanner. The MRI stereoscope takes advantage of commonly used display equipment, the MRI head coil, and a display screen. To validate the MRI stereoscope, binocular disparity stimuli were presented in a 3T MRI scanner while neural activation was recorded using functional MRI in six human participants. The comparison of large binocular disparities compared with disparities close to zero evoked strong responses across dorsal and ventral ext...

Background: Myelination proceeds sequentially in the developing postnatal human brain. It has been proposed that children with developmental delay (DD) have a temporal delay of this pattern. However, there are no controlled, blinded studies comparing the development of myelination in normal and DD children. Hypothesis: Delays in subcortical myelination accompany DD. Methods: Chart review identified 106 children (36 controls, 70 DD) aged 17-46 months. All children had a brain MRI for evaluation of DD or for another condition (controls). DD was defined as psychomotor retardation diagnosed by clinical examination and/or psychometric testing; only children with idiopathic DD were included. Children with diseases that affect white matter (sickle cell disease, leukodystrophies, etc) or overt intracranial lesions/malformations were excluded. Three board-certified pediatric neuroradiologists who were blinded to the patients’ diagnoses and to each others readings examined axial T2-weighted images. Two scoring syste...

We are using manganese-enhanced Magnetic Resonance Imaging (ME-MRI) to visualize the brains of crayfish. Manganese, a paramagnetic contrast agent and calcium analog, can highlight specific brain areas that are active. Several vertebrate studies show that ME-MRI is directly sensitive to calcium-dependent neuronal activity and can also be used to trace neuronal connections within the brain. Moreover, due to the slow clearing rate of manganese from the stimulated region of the brain, ME-MRI allows the application of the contrast agent and the sensory stimulation to take place outside the magnet before the animal is imaged. Vertebrate studies using ME-MRI are complicated by the fact that manganese does not easily pass through the blood-brain barrier, which requires intravenous infusion of the contrast agent over a long period of time in combination with injection of a hyperosmolar agent. Furthermore, vertebrates are usually anesthetized during ME-MRI studies, which reduces brain activity and makes manganese a ...

The urge to use drugs (craving) is an important factor in relapse to drug abuse. In heroin dependent patients, treatment with an opiate agonist(methadone maintenance, MM) is effective in preventing opiate withdrawal symptoms, however some MM patients continue experiencing drug craving. Data indicate that such craving may be a response to conditioned drug-related stimuli. Arterial Spin Labeled (ASL) functional MRI (fMRI) is a perfusion-weighted technique which has practical advantages over both PET and BOLD fMRI for the study of the regional cerebal blood flow (rCBF) changes during sustained cognitive states, such as cue-induced drug craving. In an ongoing study (target N = 20), MM patients (9)and controls (7) viewed non-drug and heroin-related videos (10 min each) while undergoing multi-slice ASL fMRI. Statistical parametric mapping (SPM99) was used to compare rCBF during heroin cues with baseline and correlate refional with subjective and physiological measurements of desire to use opiates. Preliminary an...