Ronald R. Price

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.

Quality assurance methods and phantoms for magnetic resonance imaging: report of AAPM nuclear magnetic resonance Task Group No. 1.

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Diffusion-weighted imaging of inflammatory myopathies: Polymyositis and dermatomyositis

Muscles of myositis patients examined with MRI demonstrate heterogeneous pathology ranging from unaffected muscle groups to severe inflammation, fat infiltration, and eventually, more serious fat replacement. The purpose of this investigation was to characterize myositic thigh muscles using diffusion‐weighted imaging (DWI) and to examine fluid motion at various disease stages. We chose to characterize total fluid motion within the muscle using the model proposed by Le Bihan et al (6,7) in which the apparent diffusion coefficient (ADC), diffusion in the extra‐ and intracellular muscle compartments (D), perfusion in capillaries (pseudodiffusion) (D*), and volume fraction of capillary perfusion (f) are determined. Unaffected patient muscles have DWI coefficients equivalent to those of normal muscles. Inflamed muscles show elevated ADC and D values compared to normal muscles (P < 0.0005), and fat‐infiltrated muscles have lower values than control muscles (P < 0.001). Inflamed muscles have lower f values than unaffected muscles (P < 0.009), suggesting decreased fractional volume of capillary perfusion. DWI provides quantitative data on molecular fluid motion in diseased muscles and affords the potential for longitudinal monitoring of myositic patients. J. Magn. Reson. Imaging 2007.

Phantom validation of coregistration of PET and CT for image-guided radiotherapy

Radiotherapy treatment planning integrating positron emission tomography (PET) and computerized tomography (CT) is rapidly gaining acceptance in the clinical setting. Although hybrid systems are available, often the planning CT is acquired on a dedicated system separate from the PET scanner. A limiting factor to using PET data becomes the accuracy of the CT/PET registration. In this work, we use phantom and patient validation to demonstrate a general method for assessing the accuracy of CT/PET image registration and apply it to two multi-modality image registration programs. An IAEA (International Atomic Energy Association) brain phantom and an anthropomorphic head phantom were used. Internal volumes and externally mounted fiducial markers were filled with CT contrast and 18F-fluorodeoxyglucose (FDG). CT, PET emission, and PET transmission images were acquired and registered using two different image registration algorithms. CT/PET Fusion (GE Medical Systems, Milwaukee, WI) is commercially available and uses a semi-automated initial step followed by manual adjustment. Automatic Mutual Information-based Registration (AMIR), developed at our institution, is fully automated and exhibits no variation between repeated registrations. Registration was performed using distinct phantom structures; assessment of accuracy was determined from registration of the calculated centroids of a set of fiducial markers. By comparing structure-based registration with fiducial-based registration, target registration error (TRE) was computed at each point in a three-dimensional (3D) grid that spans the image volume. Identical methods were also applied to patient data to assess CT/PET registration accuracy. Accuracy was calculated as the mean with standard deviation of the TRE for every point in the 3D grid. Overall TRE values for the IAEA brain phantom are: CT/PET Fusion = 1.71 +/- 0.62 mm, AMIR = 1.13 +/- 0.53 mm; overall TRE values for the anthropomorphic head phantom are: CT/PET Fusion = 1.66 +/- 0.53 mm, AMIR = 1.15 +/- 0.48 mm. Precision (repeatability by a single user) measured for CT/PET Fusion: IAEA phantom = 1.59 +/- 0.67 mm and anthropomorphic head phantom = 1.63 +/- 0.52 mm. (AMIR has exact precision and so no measurements are necessary.) One sample patient demonstrated the following accuracy results: CT/PET Fusion = 3.89 +/- 1.61 mm, AMIR = 2.86 +/- 0.60 mm. Semi-automatic and automatic image registration methods may be used to facilitate incorporation of PET data into radiotherapy treatment planning in relatively rigid anatomic sites, such as head and neck. The overall accuracies in phantom and patient images are < 2 mm and < 4 mm, respectively, using either registration algorithm. Registration accuracy may decrease, however, as distance from the initial registration points (CT/PET fusion) or center of the image (AMIR) increases. Additional information provided by PET may improve dose coverage to active tumor subregions and hence tumor control. This study shows that the accuracy obtained by image registration with these two methods is well suited for image-guided radiotherapy.

Resting functional MRI with temporal clustering analysis for localization of epileptic activity without EEG.

We report on the methods and initial findings of a novel noninvasive technique, resting functional magnetic resonance imaging (fMRI) with temporal clustering analysis (TCA), for localizing interictal epileptic activity. Nine subjects were studied including six temporal lobe epilepsy (TLE) patients with confirmed localization indicated by successful seizure control after resection. The remaining three subjects had standard presurgical evaluations with inconsistent results or suspected extratemporal lobe foci. Peaks of activity, presumably epileptic, were detected in all nine subjects, using the resting functional MRI with temporal clustering analysis. In all six patients who underwent resective surgery, the fMRI with temporal clustering analysis accurately determined the epileptogenic hippocampal hemisphere (P = 0.005). In the three subjects without confirmed localization, the technique determined regions of activity consistent with those determined by the presurgical assessments. Though more studies are required to validate this technique, the results demonstrate the potential of the resting fMRI with temporal clustering technique to detect and localize epileptic activity without the need for simultaneous electroencephalography (EEG). The greatest potential benefit of this technique will be in the evaluation of patients with suspected extratemporal lobe epilepsy and patients whose standard assessments are discordant.

FDG PET in the follow-up management of patients with newly diagnosed Hodgkin and non-Hodgkin lymphoma after first-line chemotherapy

PURPOSE The purpose of this study was to evaluate the accuracy of PET imaging for predicting recurrence of disease and determining fields of radiation therapy for patients with lymphoma after first-line chemotherapy. METHODS AND MATERIALS The study population included 40 patients with lymphoma, newly diagnosed, staged and treated with either chemotherapy alone or combined modality therapy at this institution. PET findings were correlated with CT findings and radiation ports. Treatment and follow-up course were analyzed to determine patterns of failure. RESULTS Twenty-eight of 40 patients (70%) were treated with chemotherapy alone, 12 of 40 (30%) were treated with combined modality therapy. Of the patients who received chemotherapy alone, 21 (75%) had a negative follow-up PET scan at the original site of disease, and 5 of these 21 (24%) recurred within the original site of disease. Of the patients who received combined modality therapy, 10 (83%) had a negative follow-up PET scan at the original site of disease and none recurred within the original site of disease. CONCLUSIONS A negative PET scan after completion of therapy does not exclude the presence of residual microscopic disease and does not indicate complete remission. A higher recurrence rate in patients who were treated with chemotherapy alone compared with combined modality therapy suggests that some of these patients may benefit from aggressive radiation therapy planned at initial staging. The radiation treatment volumes may be better planned from the initial staging PET study because a negative follow-up PET scan after chemotherapy cannot exclude residual microscopic disease.

Repeatability of a reference region model for analysis of murine DCE‐MRI data at 7T

To test the repeatability of a reference region (RR) model for the analysis of dynamic contrast‐enhanced MRI (DCE‐MRI) in a mouse model of cancer at high field.

CXCR4 Expression is Elevated in Glioblastoma Multiforme and Correlates with an Increase in Intensity and Extent of Peritumoral T2-weighted Magnetic Resonance Imaging Signal Abnormalities

OBJECTIVEWith the objective of investigating the utility of CXCR4, a chemokine receptor known to mediate glioma cell invasiveness, as a molecular marker for peritumoral disease extent in high-grade gliomas, we sought to characterize the expression profile of CXCR4 in a large panel of tumor samples and determine whether CXCR4 expression levels within glioblastoma multiforme might correlate with radiological evidence of a more extensive disease process. METHODSFreshly resected tumor tissue samples were processed for immunohistochemical and quantitative polymerase chain reaction analyses to identify and quantify expression levels of CXCR4 and its corresponding ligand CXCL12. T1 postcontrast and T2-weighted magnetic resonance imaging brain scans were used to generate voxel signal intensity histograms that were quantitatively analyzed to determine the extent and intensity of peritumoral signal abnormality as a marker of disseminated disease in the brain. RESULTSCXCR4 expression was markedly elevated in Grade III and IV tumors compared with Grade II gliomas. Significantly, when patients with glioblastoma multiforme were segregated into two groups based on CXCR4 expression level, we observed a statistically significant increase in the intensity and extent of peritumoral magnetic resonance imaging signal abnormalities associated with CXCR4 high-expressing gliomas. CONCLUSIONOur data confirm that high-grade gliomas robustly express CXCR4 and demonstrate a correlative relationship between expression levels of the CXCR4 receptor and the magnetic resonance imaging-based finding of a diffuse and more extensive disease process in the brain. CXCR4 expression status may, therefore, prove useful as a marker of disseminated disease in patients with glioblastoma multiforme.

Correlation Between Estimates of Tumor Perfusion From Microbubble Contrast-Enhanced Sonography and Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Objective. We compared measurements of tumor perfusion from microbub‐ble contrast‐enhanced sonography (MCES) and dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) in an animal tumor model. Methods. Seven mice were implanted with Lewis lung carcinoma cells on their hind limbs and imaged 14 days later with a Philips 5‐ to 7‐MHz sonography system (Philips Medical Systems, Andover, MA) and a Varian 7.0‐T MRI system (Varian, Inc, Palo Alto, CA). For sonographic imaging 100 μL of a perfluoropropane microbubble contrast agent (Definity; Bristol‐Myers Squibb Medical Imaging, Billerica, MA) was injected and allowed to reach a pseudo steady state, after which a high–mechanical index pulse was delivered to destroy the microbub‐bles within the field of view, and the replenishment of the microbubbles was imaged for 30 to 60 seconds. The MRI included acquisition of a T10 map and 35 serial T1‐weighted images (repetition time, 100 milliseconds; echo time, 3.1 milliseconds; α, 30°) after the injection of 100 μL of 0.2‐mmol/kg gadopente‐tate dimeglumine (Magnevist; Berlex, Wayne, NJ). Region‐of‐interest and voxel‐by‐voxel analyses of both data sets were performed; microbubble contrast‐enhanced sonography returned estimates of microvessel cross‐sectional area, microbubble velocity, and mean blood flow, whereas DCE‐MRI returned estimates of a perfusion‐permeability index and the extravascular extracellular volume fraction. Results. Comparing similar regions of tumor tissue seen on sonography and MRI, region‐of‐interest analyses revealed a strong (r 2 = 0.57) and significant relationship (P < .002) between the estimates of perfusion obtained by the two modalities. Conclusions. Microbubble contrast‐enhanced sonography can effectively depict intratumoral heterogeneity in preclinical xenograft models when voxel‐by‐voxel analysis is performed, and this analysis correlates with similar DCE‐MRI measurements.