David R. Pickens

Brain Areas Involved in Perception of Biological Motion

These experiments use functional magnetic resonance imaging (fMRI) to reveal neural activity uniquely associated with perception of biological motion. We isolated brain areas activated during the viewing of point-light figures, then compared those areas to regions known to be involved in coherent-motion perception and kinetic-boundary perception. Coherent motion activated a region matching previous reports of human MT/MST complex located on the temporo-parieto-occipital junction. Kinetic boundaries activated a region posterior and adjacent to human MT previously identified as the kinetic-occipital (KO) region or the lateral-occipital (LO) complex. The pattern of activation during viewing of biological motion was located within a small region on the ventral bank of the occipital extent of the superior-temporal sulcus (STS). This region is located lateral and anterior to human MT/MST, and anterior to KO. Among our observers, we localized this region more frequently in the right hemisphere than in the left. This was true regardless of whether the point-light figures were presented in the right or left hemifield. A small region in the medial cerebellum was also active when observers viewed biological-motion sequences. Consistent with earlier neuroimaging and single-unit studies, this pattern of results points to the existence of neural mechanisms specialized for analysis of the kinematics defining biological motion.

Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention

BACKGROUND & AIMS Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity, possibly related to abnormal brain-gut communication. Positron emission tomography imaging has suggested specific central nervous system (CNS) abnormalities in visceral pain processing in IBS. This study aimed to determine (1) if functional magnetic resonance imaging (fMRI) detects CNS activity during painful and nonpainful visceral stimulation; and (2) if CNS pain centers in IBS respond abnormally. METHODS fMRI was performed during nonpainful and painful rectal distention in 18 patients with IBS and 16 controls. RESULTS Rectal stimulation increased the activity of anterior cingulate (33/34), prefrontal (32/34), insular cortices (33/34), and thalamus (32/34) in most subjects. In IBS subjects, but not controls, pain led to greater activation of the anterior cingulate cortex (ACC) than did nonpainful stimuli. IBS patients had a greater number of pixels activated in the ACC and reported greater intensity of pain at 55-mm Hg distention than controls. CONCLUSIONS IBS patients activate the ACC, a critical CNS pain center, to a greater extent than controls in response to a painful rectal stimulus. Contrary to previous reports, these data suggest heightened pain sensitivity of the brain-gut axis in IBS, with a normal pattern of activation.

Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome

Background and aims: Irritable bowel syndrome (IBS) is a disorder of intestinal hypersensitivity and altered motility, exacerbated by stress. Functional magnetic resonance imaging (fMRI) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex (ACC), an area relevant to pain and emotions. Tricyclic antidepressants are effective for IBS. The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits. Secondary aims were to identify other brain regions altered by amitriptyline, and to determine if reductions in cerebral activation are greater during mental stress. Methods: Nineteen women with painful IBS were randomised to amitriptyline 50 mg or placebo for one month and then crossed over to the alternate treatment after washout. Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI. Distensions were performed alternately during auditory stress and relaxing music. Results: Rectal pain induced significant activation of the perigenual ACC, right insula, and right prefrontal cortex. Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex, but only during stress. Conclusions: The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual (limbic) anterior cingulated cortex and parietal association cortex. These reductions are only seen during stress. Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS.

Quantified Color Doppler Sonography of Tumor Vascularity in an Animal Model

This study was designed to evaluate the accuracy of a system to quantitate tumor vascularity with amplitude (power) color Doppler sonography two‐ and three‐dimensionally. The vascularity of 20 transplanted murine tumors was determined with quantitated amplitude color Doppler sonography both two‐ and three‐dimensionally and compared to tumor vascularity estimated by histologic examination. Serial examinations were performed 15, 30, 45, and 60 min after the injection of the exotoxin CM‐101 and saline solution to assess changes in tumor vascularity. Three‐dimensional amplitude color Doppler sonography best depicted the overall vascularity of tumor when compared to histologic estimation of vessel density. However, neither two‐ nor three‐dimensional amplitude color power angiography correlated well to the microvessel count, probably a reflection of the difference in the method for vessel quantification using sonographic versus histologic techniques. Three‐dimensional amplitude Doppler sonography correlated better with counts of large vessels (> 100 microm) as opposed to small vessels (> 15 microm). Time‐activity curves showed no difference in tumor flow at the times measured in the experimental group injected with CM‐101 or when compared to saline solutions in either the peripheral or central portions of the tumor. This three‐dimensional amplitude color Doppler sonographic system affords global quantification of tumor vascularity and flow that may, in turn, be useful in determining the probability of malignancy (by determination of branching patterns and vessel regularity) or tumor response or both to treatment.

Adaptive search space scaling in digital image registration

An image registration technique for application in X-ray, gamma-ray, and magnetic resonance imaging is described. The technique involves searching a real-valued, multidimensional, rectangular, symmetric space of bilinear geometrical transformations for a globally optimal transformation. Physical considerations provide theoretical limits on the search space, but the theoretically maximum allowable space is still often much larger than the smallest rectangular symmetric subspace that contains the optimal transformation. To reduce the search time, the current practice is to guess an optimal subspace from the maximum allowable space. This reduced space is then discretized and searched. An automatic technique to estimate adaptively a subspace from the maximum space during the search process itself is described. This adaptive technique is tested with two quite different types of search algorithms, namely, genetic algorithms and simulated annealing.

Quantification of tumor vascularity and flow with amplitude color Doppler sonography in an experimental model: preliminary results.

This study was designed to evaluate a system to quantitate vascularity and tumor blood flow with amplitude (power) color Doppler sonography. The vascularity of nine transplanted murine tumors was determined with quantitated amplitude color Doppler sonography and compared to tumor vascularity estimated by histologic examination. The system used seemed to provide an accurate depiction of the vascularity of tumor vis‐à‐vis histologic estimation of vessel density (r = 0.80). Time‐activity curves showed greater flow in the experimental group injected with an exotoxin than in the group injected with saline solution. Vascular density quantification with amplitude color Doppler sonography also was more accurate when an intravascular agent (such as an exotoxin) was used than when saline infusions were given. This quantification scheme may allow the development of a system to assess the probability of malignancy and to monitor tumor response to treatment on the basis of the vascularity of the mass.

Cortical activation during Braille reading is influenced by early visual experience in subjects with severe visual disability: A correlational fMRI study

Functional magnetic resonance imaging was performed on blind adults resting and reading Braille. The strongest activation was found in primary somatic sensory/motor cortex on both cortical hemispheres. Additional foci of activation were situated in the parietal, temporal, and occipital lobes where visual information is processed in sighted persons. The regions were differentiated most in the correlation of their time courses of activation with resting and reading. Differences in magnitude and expanse of activation were substantially less significant. Among the traditionally visual areas, the strength of correlation was greatest in posterior parietal cortex and moderate in occipitotemporal, lateral occipital, and primary visual cortex. It was low in secondary visual cortex as well as in dorsal and ventral inferior temporal cortex and posterior middle temporal cortex. Visual experience increased the strength of correlation in all regions except dorsal inferior temporal and posterior parietal cortex. The greatest statistically significant increase, i.e., ∼30%, was in ventral inferior temporal and posterior middle temporal cortex. In these regions, words are analyzed semantically, which may be facilitated by visual experience. In contrast, visual experience resulted in a slight, insignificant diminution of the strength of correlation in dorsal inferior temporal cortex where language is analyzed phonetically. These findings affirm that posterior temporal regions are engaged in the processing of written language. Moreover, they suggest that this function is modified by early visual experience. Furthermore, visual experience significantly strengthened the correlation of activation and Braille reading in occipital regions traditionally involved in the processing of visual features and object recognition suggesting a role for visual imagery. Hum. Brain Mapping 14:186–195, 2001.

Comparison of functional MRI image realignment tools using a computer-generated phantom

This study discusses the development of a computer‐generated phantom to compare the effects of image realignment programs on functional MRI (fMRI) pixel activation. The phantom is a whole‐head MRI volume with added random noise, activation, and motion. It allows simulation of realistic head motions with controlled areas of activation. Without motion, the phantom shows the effects of realignment on motion‐free data sets. Prior to realignment, the phantom illustrates some activation corruption due to motion. Finally, three widely used realignment packages are examined. The results showed that the most accurate algorithms are able to increase specificity through accurate realignment while maintaining sensitivity through effective resampling techniques. In fact, accurate realignment alone is not a powerful indicator of the most effective algorithm in terms of true activation. Magn Reson Med 46:510–514, 2001.

Magnetic resonance perfusion/diffusion imaging of the excised dog kidney

RATIONALE AND OBJECTIVES The authors developed a model of tissue capillary beds applicable to perfusion/diffusion imaging with magnetic resonance imaging (MRI). The model consists of a formalin-fixed excised dog kidney attached to a variable speed pump. With this system, it is possible to perfuse the kidney at selected rates. METHODS Using the intravoxel incoherent motion model (IVIM), the apparent diffusion coefficient (ADC), diffusion coefficient (D), and perfusion fraction (f) were computed for a region of interest (ROI) in the renal cortex and in the medulla of seven kidneys, one of which was injected with a vasodilator before fixation. ADC and D values were computed for both cortex and medulla. These values were normalized to zero flow and plotted against renal perfusion. The perfusion fraction f was expressed in percent and was not normalized to zero flow. RESULTS Normalized ADC and f were correlated with tissue perfusion rates using the Spearman rank-sum test (n = 18, rs greater than 0.5, P less than or equal to .02 for the standard preparation in both cortex and medulla), whereas normalized D (rs much less than 0.5) was uncorrelated for both preparations in cortex and medulla. CONCLUSIONS The isolated perfused dog kidney is a useful model of tissue capillary beds for perfusion imaging technique development. The perfusion/diffusion-related parameters ADC and f increase as flow increases in the tissues, whereas D does not.

Near-monochromatic X-ray beams produced by the free electron laser and Compton backscatter

The intense photon output of a free electron laser may be made to collide with its own high energy electron beam to create nearly monochromatic x-rays using Compton backscatter techniques. These x-rays can be used for imaging and non-imaging diagnostic and therapeutic experiments. The initial configuration of the Vanderbilt Medical Free Electron Laser (Sierra Laser Systems, Sunnyvale, CA) produces intense x-rays up to 17.9 keV, although higher energies are easily attainable through the use of frequency doubling methods, alteration of the energy of the electron beam and coupling to conventional laser inputs.