Double pulsed field gradient diffusion MRI to assess skeletal muscle microstructure.

PURPOSE: Preliminary study to determine whether double pulsed field gradient (PFG) diffusion MRI is sensitive to key features of muscle microstructure related to function. METHODS: The restricted diffusion profile of molecules in models of muscle microstructure derived from histology were systematically simulated using a numerical simulation approach. Diffusion tensor subspace imaging analysis of the diffusion signal was performed, and spherical anisotropy (SA) was calculated for each model. Linear regression was used to determine the predictive capacity of SA on the fiber area, fiber diameter, and surface area to volume ratio of the models. Additionally, a rat model of muscle hypertrophy was scanned using a single PFG and a double PFG pulse sequence, and the restricted diffusion measurements were compared with histological measurements of microstructure. RESULTS: Excellent agreement between SA and muscle fiber area (r2 = 0.71; p < 0.0001), fiber diameter (r2 = 0.83; p < 0.0001), and surface area to volume ratio (r2 = 0.97; p < 0.0001) in simulated models was found. In a scanned rat leg, the distribution of these microstructural features measured from histology was broad and demonstrated that there is a wide variance in the microstructural features observed, similar to the SA distributions. However, the distribution of fractional anisotropy measurements in the same tissue was narrow. CONCLUSIONS: This study demonstrates that SA-a scalar value from diffusion tensor subspace imaging analysis-is highly sensitive to muscle microstructural features predictive of function. Furthermore, these techniques and analysis tools can be translated to real experiments in skeletal muscle. The increased dynamic range of SA compared with fractional anisotropy in the same tissue suggests increased sensitivity to detecting changes in tissue microstructure.

Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer's disease supports retrogenesis.

The retrogenesis model of Alzheimer's disease (AD) posits that white matter (WM) degeneration follows a pattern that is the reverse of myelogenesis. Using diffusion tensor imaging (DTI) to test this model, we predicted greater loss of microstructural integrity in late-myelinating WM fiber pathways in AD patients than in healthy older adults, whereas differences in early-myelinating WM fiber pathways were not expected. We compared 16 AD patients and 14 demographically-matched healthy older adults with a whole-brain approach via tract-based spatial statistics (TBSS), and a region of interest (ROI) approach targeting early-myelinating (posterior limb of internal capsule, cerebral peduncles) and late-myelinating (inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF]) fiber pathways. Permutation-based voxelwise analysis supported the retrogenesis model. There was significantly lower fractional anisotropy (FA) in AD patients compared to healthy older adults in late-myelinating but not early-myelinating pathways. These group differences appeared to be driven by loss of myelin integrity based on our finding of greater radial diffusion in AD than in healthy elderly. ROI analyses were generally in agreement with whole-brain findings, with significantly lower FA and increased radial diffusion in the ILF in the AD group. Consistent with the retrogenesis model, AD patients showed demonstrable changes in late-myelinating WM fiber pathways. Given greater change in the ILF than the SLF, wallerian degeneration secondary to cortical atrophy may also be a contributing mechanism. Knowledge of the pattern of WM microstructural changes in AD and its underlying mechanisms may contribute to earlier detection and intervention in at-risk groups.

Projective imaging of pulsatile flow with magnetic resonance.

Noninvasive angiography with magnetic resonance is demonstrated. Signal arising in all structures except vessels that carry pulsatile flow is eliminated by means of velocity-dependent phase contrast, electrocardiographic gating, and image subtraction. Background structures become in effect transparent, enabling the three-dimensional vascular tree to be imaged by projection to a two-dimensional image plane. Image acquisition and processing are accomplished with entirely conventional two-dimensional Fourier transform magnetic resonance imaging techniques. When imaged at 0.6 tesla, vessels 1 to 2 millimeters in diameter are routinely detected in a 50-centimeter field of view with data acquisition times less than 15 minutes. Studies of normal and pathologic anatomy are illustrated in human subjects.

Involvement of striate and extrastriate visual cortical areas in spatial attention.

We investigated the cortical mechanisms of visual-spatial attention while subjects discriminated patterned targets within distractor arrays. Functional magnetic resonance imaging (fMRI) was used to map the boundaries of retinotopic visual areas and to localize attention-related changes in neural activity within several of those areas, including primary visual (striate) cortex. Event-related potentials (ERPs) and modeling of their neural sources, however, indicated that the initial sensory input to striate cortex at 50-55 milliseconds after the stimulus was not modulated by attention. The earliest facilitation of attended signals was observed in extrastriate visual areas, at 70-75 milliseconds. We hypothesize that the striate cortex modulation found with fMRI may represent a delayed, re-entrant feedback from higher visual areas or a sustained biasing of striate cortical neurons during attention. ERP recordings provide critical temporal information for analyzing the functional neuroanatomy of visual attention.

A model for the coupling between cerebral blood flow and oxygen metabolism during neural stimulation.

A general mathematical model for the delivery of O2 to the brain is presented, based on the assumptions that all of the brain capillaries are perfused at rest and that all of the oxygen extracted from the capillaries is metabolized. The model predicts that disproportionately large changes in blood flow are required in order to support small changes in the O2 metabolic rate. Interpreted in terms of this model, previous positron emission tomography (PET) studies of the human brain during neural stimulation demonstrating that cerebral blood flow (CBF) increases much more than the oxygen metabolic rate are consistent with tight coupling of flow and oxidative metabolism. The model provides a basis for the quantitative interpretation of functional magnetic resonance imaging (fMRI) studies in terms of changes in local CBF.

Sleep deprivation, EEG, and functional MRI in depression: preliminary results.

One night of total or partial sleep deprivation (SD) produces temporary remissions in 40-60% of patients with major depression. Two unmedicated patients with major depression and a matched control received quantitative perfusion MR images at baseline and after one night of partial SD (PSD). A reduction > or =30% in the 17-item Hamilton Depression Rating Scale (omitting sleep and weight loss items) defined antidepressant response. Theory, techniques, strengths and weaknesses of quantitative perfusion MRI are described in detail. At baseline, the responder exhibited elevated perfusion covering ventral anterior cingulate/medial frontal cortex; the control's maximal perfusion area was markedly smaller. The nonresponder's perfusion was lowest of all, particularly ventrally. PSD decreased perfusion over much of the responder's hyperperfused area but did not change the nonresponder's scan. These preliminary findings are consistent with previous SD studies using PET and SPECT.

Theoretical considerations and in vitro results for the development of percutaneous transcatheter balloon embolectomy.

RATIONALE AND OBJECTIVES: To prove the feasibility of performing percutaneous transcatheter embolectomy using a funnel-shaped catheter tip and balloon embolectomy catheters. METHODS: A theoretical model is described to assess the influence of the diameter of an introductory device and coaxially introduced embolectomy catheter. A funnel-shaped catheter tip was attached to 7F, 8F, and 9F introductory sheaths. In vitro embolectomy of 5 g and 12 g thrombi was performed with 3F and 4F embolectomy catheters. RESULTS: The number of extractions required was significantly related to the ratio of the diameters of the sheaths and embolectomy catheter shafts. The combination of a 7F sheath with a 4F embolectomy catheter required the greatest number of extractions (8.4 +/- 1.7). The least number of extractions was needed for the combination of a 9F sheath with 4F and 3F embolectomy catheters (1.6 +/- 0.7 and 1.8 +/- 0.4, respectively). CONCLUSIONS: Our results indicate that percutaneous embolectomy with balloon embolectomy catheters is feasible. However, further research is necessary before the final catheter design is chosen.

Evaluation of nitrobenzimidazoles as hypoxic cell radiosensitizers.

Radiobiological and pharmacokinetic assays were performed to determine the potential of 2-nitrobenzimidazole (NBI) as a hypoxic cell radiosensitizing agent. As judged by comparing survival curve slopes of Serratia marcescens irradiated under aerated and hypoxic conditions, the NBI enhancement ratio (ER) at 2 mM concentration was 2.4 +/- 0.2, compared with an oxygen enhancement ratio of 3.3 +/- 0.3. 2,5-Dinitrobenzimidazole (DNBI) was investigated in vitro; its ER was 3.0 +/- 0.3 at 4 mM concentration. Very poor tissue penetration of DNBI precluded further testing in vivo. Acute toxic signs appeared in C3H/HeJ mice following ip injection of NBI at 100 mg/kg. These would be partly attributable to the stress caused by the high pH of the injection vehicle. The LD50 was estimated to be 125-150 mg/kg. Mammary adenocarcinoma tumors grown in the flanks of these mice exhibited maximum NBI levels at 5 min postinjection (ip). Peak tumor radiosensitization occurred in the interval between 5 and 10 min postinjection. The ER for tumor regrowth delay was 2.1 +/- 0.3 following 50 mg/kg injected into mice 5 min before irradiation. Functional evaluation up to 40 days after treatment revealed no evidence of neurological deficit.

Local perfusion and metabolic demand during exercise: a noninvasive MRI method of assessment.

A noninvasive magnetic resonance imaging (MRI) method to assess the distribution of perfusion and metabolic demand (Q/VO(2)) in exercising human skeletal muscle is described. This method combines two MRI techniques that can provide accurate multiple localized measurements of Q/VO(2) during steady-state plantar flexion exercise. The first technique, (31)P chemical shift imaging, permits the acquisition of comparable phosphorus spectra from multiple voxels simultaneously. Because phosphocreatine (PCr) depletion is directly proportional to ATP hydrolysis, its relative depletion can be used as an index of muscle O(2) uptake (VO(2)). The second MRI technique allows the measurement of both spatially and temporally resolved muscle perfusion in vivo by using arterial spin labeling. Promising validity and reliability data are presented for both MRI techniques. Initial results from the combined method provide evidence of a large variation in Q/VO(2), revealing areas of apparent under- and overperfusion for a given metabolic turnover. Analysis of these data in a similar fashion to that employed in the assessment of ventilation-to-perfusion matching in the lungs revealed a similar second moment of the perfusion distribution and PCr distribution on a log scale (log SD(Q) and log SD(PCr)) (0.47). Modeling the effect of variations in log SD(Q) and log SD(PCr) in terms of attainable VO(2), assuming no diffusion limits, indicates that the log SD(Q) and log SD(PCr) would allow only 92% of the target VO(2) to be achieved. This communication documents this novel, noninvasive method for assessing Q/VO(2), and initial data suggest that the mismatch in Q/VO(2) may play a significant role in determining O(2) transport and utilization during exercise.

Blood flow dynamics in the vertebrobasilar system: correlation of a transparent elastic model and MR angiography.

PURPOSE: To describe the flow patterns in a model of the vertebrobasilar artery and use these observations to explain the appearance of the flow on the MR images. METHODS: We created an anatomically precise, transparent elastic model of the human vertebrobasilar artery containing a basilar tip aneurysm and perfused the model with non-Newtonian fluid which has similar rheologic properties to blood. Flow patterns in the vessels were directly observed. MR angiogram images were obtained with commercially available two-dimensional time-of-flight, three-dimensional time-of-flight, and 3-D phase-contrast MR angiographic pulse sequences, and they were correlated with the directly seen flow patterns. Quantitative flow velocity measurements were performed with 2-D cine phase-contrast MR angiography and correlated with the flow measured with an electromagnetic flow meter. RESULTS: Visualization studies showed the dye stream patterns in the vertebrobasilar arteries to be extremely complex and variable. During the MR experiments we found that often the same segment of a vessel could appear very different depending on the pulse sequence. In some instances, the model experiments helped to explain the MR appearance of the vessels. Flow profiles measured with 2-D cine phase contrast were found to be consistent with those measured directly with an electromagnetic flow meter. CONCLUSION: Clear elastic models can be used to duplicate the flow in human cranial vessels and thus provide a unique means to observe these flow patterns directly. The flow patterns helped to explain the variation in appearance of the vessels and the artifacts with different MR angiography pulse sequences. The artifacts depend on both the geometry of the vessel and the flow pattern within it. Two-dimensional cine phase-contrast MR provides temporal flow field information that is directly related to physiological information about flow volumes and velocity patterns.

Mapping the physiological parameters of articular cartilage with magnetic resonance imaging.

The ability of magnetic resonance imaging (MRI) to visualize the spatial distribution of parameters related to the physiological and structural properties of tissues makes it an ideal tool for the study of articular cartilage. A variety of ingenious MRI methods have been devised to probe the complex composition and biochemistry of normal and degenerate articular cartilage. In this article we review the current status of this research and pose some questions concerning the future directions of articular cartilage research and clinical applications.

Quantitative perfusion imaging using arterial spin labeling.

Arterial spine labeling (ASL) techniques have matured to the point that they can provide robust quantitative multislice measurements of cerebral blood flow (CBF) under most circumstances. These techniques provide better spatial and temporal resolution than positron-emission tomography (PET) and are entirely noninvasive, requiring no injections or radiation. The most obvious clinical application is in the evaluation of acute stroke, in which the primary pathology is a lack of CBF, precisely the quantity that is measured directly by ASL. The one major technical challenge that currently prevents more general application in the brain is the sensitivity to abnormally long transit delays.

Fertility of broiler breeders following categorization by the OptiBreed sperm quality index when hens are inseminated with a constant number of sperm.

If semen quality was known prior to insemination, sperm doses could possibly be decreased, maximizing the number of hens inseminated. The sperm quality index (SQI), an indicator of overall semen quality, is determined by the number of deflections in a light path due to sperm movement inside a capillary tube. The objectives of this study were 1) to determine the age at which the SQI becomes a static predictor of semen quality and 2) to determine if fertility of males with a higher SQI responds more favorably to insemination dose reduction than that of males with a lower SQI. Weekly from 23 to 32 wk of age, 144 Cobb males were tested for SQI. At 32 wk of age, males were placed into four groups that represented the SQI population quartiles as follows: poor, fair, good, and best. A fifth SQI group, uncategorized, was created to determine fertility of the original population by mixing equal amounts of semen from each of the four groups. Semen was collected weekly from 33 to 40 wk of age from 18 males in each of the four groups, pooled by group, and used to inseminate 30 hens per group with 50 or 100 million sperm. Eggs were collected daily, incubated, and broken out to determine fertility. Correlation coefficients between weekly SQI results and overall averages for individual males indicated that the SQI stabilized after the birds were 28 wk of age. The main effect for SQI selection revealed that the best SQI group had the highest fertility (88%), which did not differ from the good (83%) or fair group (82%) but was greater than the uncategorized group (80%). Fertilities of the top three groups and the uncategorized group were higher than the poor group (63%) (P < 0.0001, SEM 2.18). In addition, there was an interaction between SQI classification and insemination dose. Fertilities of the top three SQI groups were similar at the 50 and 100 million sperm doses. However, the poor and uncategorized SQI groups had lower fertility at the 50 million dose as compared to the 100 million dose. By categorizing males into SQI groups after 28 wk of age, insemination dose can be reduced, maximizing a male's fertilizing potential.

Is MAST in the past? The pros and cons of MAST usage in the field.

Initially, MAST was viewed as a panacea for hypovolemic trauma patients. Through decades of study, this has not panned out. However, MAST seems to stabilize and decrease bleeding in pelvic and long-bone fractures of the lower extremities. It also appears useful in anaphylaxis and in non-traumatic intra-abdominal hemorrhage. The suit has proven deleterious to trauma victims with moderate hypotension (systolic BP 50-90 mm Hg) who face only a short ride to a hospital, especially those with thoracic injuries. Its role in patients with severe hypotension or long prehospital transport times remains unclear. In severely hypotensive patients, the improvement in BP and oxygenation to the heart and brain may override any negative effects of continued hemorrhage. We must wait for further studies to resolve these issues.

White matter integrity in adolescents with histories of marijuana use and binge drinking.

Structural brain abnormalities have been observed in adolescents with alcohol use disorders but less is known about neuropathological brain characteristics of teens with sub-diagnostic binge drinking or the common pattern of binge drinking combined with marijuana use. The goal of this study was to examine white matter integrity in adolescents with histories of binge drinking and marijuana use. Diffusion tensor imaging (DTI) was conducted with 42 adolescents (ages 16-19) classified as controls, binge drinkers, or binge drinkers who are also heavy marijuana users. Tract based spatial analysis identified shared fiber structure across individuals and facilitated voxelwise comparisons of fractional anisotropy (FA) and mean diffusivity (MD) between groups. Significant between group differences were found in FA in eight white matter regions (ps < or = .016) between the binge drink-only group and controls, including superior corona radiata, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and superior longitudinal fasciculus. Interestingly, in 4 of these same regions, binge drinkers who are also heavy marijuana users had higher FA than binge drinkers who did not use marijuana (ps<.05). MD did not differ between groups. Findings are largely consistent with research suggesting less neuropathology in adolescents without histories of substance use. However, binge drinkers who also use marijuana did not show as consistent a divergence from non-users as did the binge drink-only group. Detection of white matter alterations may have implications in identifying early cognitive dysfunction in substance using adolescents.

The policies and practices of American psychiatry are oppressive.

The author argues that psychiatry is not a medical specialty but an instrument for the social control of people whose ideas, actions, values, and life-styles threaten or disrupt established power relationships within families, communities, or society. Psychiatry's instruments for social control are involuntary incarceration and so-called treatment in facilities in which inmates are brutalized, harassed, neglected, and humiliated. The major somatic psychiatric treatments--drugs, electroconvulsive therapy (ECT), and lobotomy--have produced an epidemic of neurological and brain dysfunction, such as tardive dyskinesia, associated with neuroleptic drugs, and memory impairment, associated with ECT. The author condemns the freezing experiments conducted on psychiatric inmates in the United States and on concentration-camp inmates in Germany during the 1940s.

Anisotropy in high angular resolution diffusion-weighted MRI.

The diffusion in voxels with multidirectional fibers can be quite complicated and not necessarily well characterized by the standard diffusion tensor model. High angular resolution diffusion-weighted acquisitions have recently been proposed as a method to investigate such voxels, but the reconstruction methods proposed require sophisticated estimation schemes. We present here a simple algorithm for the identification of diffusion anisotropy based upon the variance of the estimated apparent diffusion coefficient (ADC) as a function of measurement direction. The rationale for this method is discussed, and results in normal human subjects acquired with a novel diffusion-weighted stimulated-echo spiral acquisition are presented which distinguish areas of anisotropy that are not apparent in the relative anisotropy maps derived from the standard diffusion tensor model. Published 2001 Wiley-Liss, Inc.

Distortions from curved flow in magnetic resonance imaging.

We present an analysis of how vessel curvature can create distortions in magnetic resonance images of flowing blood. Steady flow in curved vessels produces distortions of the vessel shape and intensity variations in the image due to motion during the interval between phase encoding or slice selection and the echo center. Even with steady flow, vessel curvature produces motion moments higher than velocity (acceleration, etc.), but use of a first order oblique flow compensated phase encoding gradient waveform reduced the distortion in the image. Numerical calculations of image distortions based on simple flow models are in good agreement with experimental results in a phantom.

Liquid chromatographic determination of lasalocid sodium in chicken skin: interlaboratory study.

The U.S. Food and Drug Administration (FDA) sponsored an interlaboratory study of a liquid chromatographic determinative procedure for lasalocid sodium in chicken skin with adhering fat. Four laboratories analyzed 35 dosed tissue samples and 82 fortified tissue samples containing lasalocid at levels ranging from 0.1 to 0.6 ppm. Samples were homogenized with acetonitrile, washed with hexane, and partitioned into the mobile phase prior to analysis liquid chromatography with fluorescence detection. The results of the interlaboratory study showed good reproducibility for fortified samples. Fortification levels, average recoveries, and interlaboratory percent coefficients of variation were as follows: 0.6 ppm, 0.57 ppm, and 9.7; 0.3 ppm, 0.25 ppm, and 9.1; and 0.15 ppm, 0.14 ppm, and 7.0, respectively. Data for analysis of the dosed tissue also showed good agreement among the laboratories.