P.W. Stroman

Mapping of neuronal function in the healthy and injured human spinal cord with spinal fMRI.

Functional magnetic resonance imaging of the human spinal cord is carried out with a graded thermal stimulus in order to establish the relationship between signal changes and neural activity. Studies of the lumbar spinal cord in 15 healthy subjects with 10 degrees C stimulation of the skin overlying the calf demonstrate a pattern of activity that matches the neuronal anatomy of the spinal cord. This pattern shows primarily dorsal horn activity, with expected components of motor reflex activity as well. Moreover, a later response shifting to noxious cold over time is also demonstrated with a shift to more dorsal horn activity. Signal intensity changes detected at different degrees of thermal stimulation have a biphasic nature, with much larger signal changes below 15 degrees C as the stimulus becomes noxious, and agree well with electrophysiological results reported in the literature. These findings demonstrate a strong correspondence between Spinal fMRI results and neural activity in the human spinal cord. Spinal fMRI is also applied to studies of the injured spinal cord, below the site of injury. Results consistently demonstrate activity in the spinal cord even when the subjects cannot feel the stimulus being applied. Signal intensity changes demonstrate the same stimulus-response pattern as that in noninjured subjects, but the areas of activity in the spinal gray matter are notably altered. In subjects with complete injuries, activity is absent ipsilateral to the thermal stimulation, but appears to be enhanced on the contralateral side. These findings demonstrate the reliability of Spinal fMRI and its clinical potential.

Extravascular proton-density changes as a non-BOLD component of contrast in fMRI of the human spinal cord.

The fractional signal intensity change (ΔS/S) observed during activation in T2‐weighted fMRI of the spinal cord has previously been shown to depend linearly on the echo time (TE) but to have a positive value of roughly 2.5% extrapolated to zero TE. In this study we investigated the origin of this finding by measuring the ΔS/S in spinal fMRI with very short TEs. Our results demonstrate that the ΔS/S does not approach zero, but has a value as high as 3.3% at TE = 11 ms. At TEs > 33 ms we observed the linear relationship between ΔS/S and TE as in previous studies. These data demonstrate that there is a non‐BOLD contribution to signal changes observed in spinal fMRI. We hypothesize that this contribution is a local proton density increase due to increased water exudation from capillaries with increased blood flow during neuronal activation, and term this effect “signal enhancement by extravascular protons” (SEEP). Magn Reson Med 48:122–127, 2002.

BOLD MRI of the human cervical spinal cord at 3 tesla.

The feasibility of functional MRI of the spinal cord was investigated by carrying out blood oxygen‐level dependent (BOLD) imaging of the human cervical spinal cord at a field of 3 T. BOLD imaging of the cervical spinal cord showed an average intensity increase of 7.0% during repeated exercise with the dominant hand with a return to baseline during rest periods. The areas of activation were predominantly on the same side of the spinal cord as the hand performing the exercise, between the levels of the sixth cervical and first thoracic spinal cord segments. The direct correspondence between these areas and those involved with the transmission of motor impulses to the hand, and reception of sensory information from the hand, demonstrates that spinal functional magnetic resonance imaging is feasible. Magn Reson Med 42:571–576, 1999.

Functional MRI of motor and sensory activation in the human spinal cord

MR imaging of the cervical spinal cord was carried out on volunteers during alternated rest and either motor or sensory stimulation of one hand, in order to detect image intensity changes arising concomitant to neuronal activity. We employed both spin-echo and gradient-echo echo-planar imaging, on the right and left hands, with both symmetric and asymmetric temporal patterns of rest and stimulation. Intensity changes correlated with the time course of stimulation were consistently detected, and the magnitude of the intensity changes depended on the duration of stimulation. The activated regions in the spinal cord extended along a column on the side of the body being stimulated and included localized regions on the contralateral side, in agreement with the neural anatomy.

Functional magnetic resonance imaging of the human brain based on signal enhancement by extravascular protons (SEEP fMRI).

Functional magnetic resonance imaging (fMRI) studies of the human brain were carried out at 3 Tesla to investigate an fMRI contrast mechanism that does not arise from the blood oxygen‐level dependent (BOLD) effect. This contrast mechanism, signal enhancement by extravascular protons (SEEP), involves only proton‐density changes and was recently demonstrated to contribute to fMRI signal changes in the spinal cord. In the present study it is hypothesized that SEEP fMRI can be used to identify areas of neuronal activity in the brain with as much sensitivity and precision as can be achieved with BOLD fMRI. A detailed analysis of the areas of activity, signal intensity time courses, and the contrast‐to‐noise ratio (CNR), is also presented and compared with the BOLD fMRI results. Experiments were carried out with subjects performing a simple finger‐touching task, or observing an alternating checkerboard pattern. Data were acquired using a conventional BOLD fMRI method (gradient‐echo (GE) EPI, TE = 30 ms), a conventional method with reduced BOLD sensitivity (GE‐EPI, TE = 12 ms), and SEEP fMRI (spin‐echo (SE) EPI, TE = 22 ms). The results of this study demonstrate that SEEP fMRI may provide better spatial localization of areas of neuronal activity, and a higher CNR than conventional BOLD fMRI, and has the added benefit of lower sensitivity to field inhomogeneities. Magn Reson Med 49:433–439, 2003.

Functional magnetic resonance imaging of the human cervical spinal cord with stimulation of different sensory dermatomes

Functional MR imaging (fMRI) of the cervical spinal cord was carried out in 13 healthy volunteers. A cold stimulus was applied, at different times, to three different sensory dermatome regions overlying the right hand and forearm: the thumb side of the palm, the little finger side of the palm, and the forearm below the elbow. Stimulation of these areas is expected to involve the 6(th), 8(th), and 5(th) cervical spinal cord segments respectively. Whereas true activations are expected to correspond to the region being stimulated, false activations such as arising from noise and motion, are not. The results demonstrate that clustering of active pixels into groups based on their intensity time courses discriminates false activations from true activations. Following clustering, the distribution of activity observed with fMRI matched the expected regions of neuronal activation with the different areas of stimulation on the hand and forearm.

Functional MRI of the rat lumbar spinal cord involving painful stimulation and the effect of peripheral joint mobilization

To examine neuronal activation in the spinal cord due to secondary hyperalgesia resulting from intrajoint capsaicin injection, and the effect of physiotherapy manipulation, using functional magnetic resonance imaging (fMRI), in α‐chloralose anesthetized rats.

Characterization of contrast changes in functional MRI of the human spinal cord at 1.5 T

Contrast changes observed in functional magnetic resonance imaging in the human spinal cord were investigated with both motor and sensory tasks over a range of echo times. Data were acquired using a single-shot fast spin-echo sequence at 1.5 Tesla. Data were analyzed with two different correlation thresholds and the effects of altering the order of repeated experiments was also investigated. Plots of the fractional signal change as a function of echo time yielded linear functions with slopes corresponding to relaxation rate changes of -0.30 sec(-1) with sensory stimulation and approximately -0.50 sec(-1) with a motor task. However, the fractional signal change extrapolated to an echo time of zero was significantly greater than zero in each case and was roughly 2.5%. This suggests that in addition to the BOLD effect there is a baseline signal change which occurs concomitant to neuronal activation in the spinal cord.

Pain modulates cerebral activity during cognitive performance

The present study investigates how pain modulates brain activity during the performance of a semantic cognitive task. Based on previous observations, we hypothesized that a simultaneous painful stimulus will induce an activation increase in brain regions engaged in the cognitive task. High-field BOLD-fMRI experiments were conducted on 12 young healthy subjects, using a 2 x 2 factorial design. Painful stimuli were induced by thermal hot stimulation (46-49 degrees C) on the palmar surface of the hand, using a contact thermode. Cognitive tasks consisted of either word generation (category fluency) or word repetition. Brain activity owing to the semantic tasks in the group was highly consistent with previous neuroimaging studies. When the painful stimulus was added to the cognitive task, activity in brain regions involved in semantic cognition, such as Brocas area, was increased (P < 0.01). Pain also modulated activity in brain areas not directly engaged in cognition. A positive modulation effect was observed in the midcingulate and the dorsomedial prefrontal cortex (P < 0.05). A negative modulation effect was observed in perigenual cingulate cortex, insula, and medial thalamus (P < 0.05).

Spin-echo versus gradient-echo fMRI with short echo times

Blood-oxygen level dependent signal changes in the visual cortex were investigated as a function of echo time with spin-echo and gradient-echo EPI at 1.5 T and 3 T. The linear relationship between the fractional signal change and the echo time was apparent in all cases. Relaxation rate changes determined from the slope of this linear relation agree with published values, intercept values extrapolated to an echo time of zero, however, were 0.66% to 1.0% with spin-echo EPI, and 0.11% to 0.35% with gradient-echo EPI. Spin-echo and gradient-echo EPI can therefore yield similar signal changes at sufficiently short echo times.