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Biomedical subjects

J Mayhew

Publications and source records attributed to J Mayhew.

At least 19 recordsLinked to original sources

Clinical evaluator reliability for quantitative and manual muscle testing measures of strength in children.

Measurements of muscle strength in clinical trials of Duchenne muscular dystrophy have relied heavily on manual muscle testing (MMT). The high level of intra- and interrater variability of MMT compromises clinical study results. We compared the reliability of 12 clinical evaluators in performing MMT and quantitative muscle testing (QMT) on 12 children with muscular dystrophy. QMT was reliable, with an interclass correlation coefficient (ICC) of >0.9 for biceps and grip strength, and >0.8 for quadriceps strength. Training of both subjects and evaluators was easily accomplished. MMT was not as reliable, and required repeated training of evaluators to bring all groups to an ICC >0.75 for shoulder abduction, elbow and hip flexion, knee extension, and ankle dorsiflexion. We conclude that QMT shows greater reliability and is easier to implement than MMT. Consequently, QMT will be a superior measure of strength for use in pediatric, neuromuscular, multicenter clinical trials.

Child↗

Signal source separation in the analysis of neural activity in brain.

This research examines the spatial and temporal characteristics of the responses to stimulation of the barrel cortex in anesthetized rats using optical imaging with particular emphasis on methods of analysis which reduce the effects of low-frequency oscillations on localization of the activated cortical region. Image sequences were captured using a light source with a narrow bandwidth of wavelength (590 +/- 2 nm). On each trial image data were collected at 15 Hz and stored over a 12-s period starting 8 s before stimulation onset. Stimulation was for 1 s using an oscillating whisker vibrator (approximately 1-mm deflection at 5 Hz). For each subject a total of 30 experimental trials were collected and averaged. There was an interstimulus interval of 26 s. The trial-averaged data were analyzed using two related signal source separation algorithms. Both algorithms use a weak model of the expected temporal response as a filter to exclude contributions from low-frequency baseline oscillations which we call the V-signal. We found that both algorithms successfully separated most of the effects of the V-signal from the response to the stimulation. The performance of the algorithms compared favorably with the performance of related algorithms without weak constraints and the "ratio of means" strategy used by C. H. Chen-Bee et al. (1996b, J. Neurosci. Methods 68:28-37; C. H. Chen-Bee et al., 2000, J. Neurosci. Methods 97:157-173).

Algorithms↗

Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex.

Optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) data sequences from anesthetized rats were used to determine the relationship between changes in oxy-and deoxygenated hemoglobin concentration and changes in blood volume and flow in the presence and absence of stimulation. The data from Jones et al. (accompanying paper) were used to explore the differences between two theoretical models of flow activation coupling. The essential difference between the two models is the extension of the model of Buxton and Frank by Hyder et al. (1998, J. Appl. Physiol. 85: 554--564) to incorporate change in capillary diffusivity coupled to flow. In both models activation-increased flow changes increase oxygen transport from the capillary; however, in Hyder et al.'s model the diffusivity of the capillary itself is increased. Hyder et al. proposed a parameter (Omega), a scaling "constant" linking increased blood flow and oxygen "diffusivity" in the capillary bed. Thus, in Buxton and Frank's theory, Omega = 0; i.e., there are no changes in diffusivity. In Hyder et al.'s theory, 0 < Omega < 1, and changes in diffusivity are assumed to be linearly related to flow changes. We elaborate the theoretical position of both models to show that, in principle, the different predictions from the two theories can be evaluated using optical imaging spectroscopy data. We find that both theoretical positions have limitations when applied to data from brief stimulation and when applied to data from mild hypercapnia. In summary, the analysis showed that although Hyder et al.'s proposal that diffusivity increased during activation did occur; it was shown to arise from an implementation of Buxton and Frank's theory under episodes of brief stimulation. The results also showed that the scaling parameter Omega is not a constant as the Hyder et al. model entails but in fact varies over the time course of the flow changes. Data from experiments in which mild hypercapnia was administered also indicated changes in the diffusivity of the capillary bed, but in this case the changes were negative; i.e., oxygen transport from the capillary decreased relative to baseline under hypercapnia. Neither of the models could account for the differences between the hypercapnia and activation data when matched for equivalent flow changes. A modification to the models to allow non-null tissue oxygen concentrations that can be moderated by changes due to increased metabolic demand following increased neural activity is proposed. This modification would allow modulation of oxygen transport from the capillary bed (e.g., changes in diffusivity) by tissue oxygen tension and would allow a degree of decoupling of flow and oxygen delivery, which can encompass both the data from stimulation and from hypercapnia.

Animals↗

Concurrent optical imaging spectroscopy and laser-Doppler flowmetry: the relationship between blood flow, oxygenation, and volume in rodent barrel cortex.

Functional magnetic resonance imaging (fMRI) is based on the coupling between neural activity and changes in the concentration of the endogenous paramagnetic contrast agent deoxygenated hemoglobin. Changes in the blood oxygen level-dependent (BOLD) signal result from a complex interplay of blood volume, flow, and oxygen consumption. Optical imaging spectroscopy (OIS) has been used to measure changes in blood volume and saturation in response to increased neural activity, while laser Doppler Flowmetry (LDF) can be used to measure flow changes and is now commonplace in neurovascular research. Here, we use concurrent OIS and LDF to examine the hemodynamic response in rodent barrel cortex using electrical stimulation of the whisker pad at varying intensities. Spectroscopic analysis showed that stimulation produced a biphasic early increase in deoxygenated hemoglobin (Hbr), followed by a decrease below baseline, reaching minima at approximately 3.7 s. There was no evidence for a corresponding early decrease in oxygenated hemoglobin (HbO(2)), which simply increased after stimulation, reaching maximum at approximately 3.2 s. The time courses of changes in blood volume (CBV) and blood flow (CBF) were similar. Both increased within a second of stimulation onset and peaked at approximately 2.7 s, after which CBV returned to baseline at a slower rate than CBF. The changes in Hbr, Hbt, and CBF were used to estimate changes in oxygen consumption (CMRO(2)), which increased within a second of stimulation and peaked approximately 2.2 s after stimulus onset. Analysis of the relative magnitudes of CBV and CBF indicates that the fractional changes of CBV could be simply scaled to match those of CBF. We found the relationship to be well approximated by CBV = CBF(0.29). A similar relationship was found using the response to elevated fraction of inspired carbon dioxide (FICO(2)).

Animals↗

Pseudo-random procedures for rapid presentation rates using optical imaging and spectroscopy.

Optical imaging of rat barrel cortex has provided detailed spatio-temporal maps of functional cortical architecture. We describe an event-related procedure (ERP) for optical imaging based on selective signal averaging as reported by Burock et al., using an anti-correlative pseudo-random event sequence. The sequence used 1 s vibrissal stimulation at 5 Hz, with an interevent interval of 2 s. This rapid presentation rate allows for greater statistical power per unit time, and allows for direct comparison of event-related studies with other imaging modalities. The spatio-temporal characteristics of single wavelength and spectrographic results were found to be comparable with those obtained by standard techniques, although a general lessening of haemodynamic response function (HRF) was noted. We also describe a method of locating barrel activity by spectral analysis of summed event data. Using this technique, the power spectrum of remitted light from the barrel region was found to peak within +/- 0.12 Hz of the inter-event interval frequency.

Algorithms↗

Spectroscopic analysis of neural activity in brain: increased oxygen consumption following activation of barrel cortex.

This research investigates the hemodynamic response to stimulation of the barrel cortex in anaesthetized rats using optical imaging and spectroscopy (Bonhoeffer and Grinvald, 1996; Malonek and Grinvald, 1996; Mayhew et al., 1999). A slit spectrograph was used to collect spectral image data sequences. These were analyzed using an algorithm that corrects for the wavelength dependency in the optical path lengths produced by the light scattering properties of tissue. The analysis produced the changes in the oxy- and deoxygenation of hemoglobin following stimulation. Two methods of stimulation were used. One method mechanically vibrated a single whisker, the other electrically stimulated the whisker pad. The electrical stimulation intensity varied from 0.4 to 1.6 mA. The hemodynamic responses to stimulation increased as a function of intensity. At 0.4 mA they were commensurate with those from the mechanical stimulation; however, the responses at the higher levels were greater by a factor of approximately 10. For both methods of data collection, the results of the spectroscopic analysis showed an early increase in deoxygenated hemoglobin (Hbr) with no evidence for a corresponding decrease in oxygenated hemoglobin (HbO(2)). Evidence for increased oxygen consumption (CMRO(2)) was obtained by converting the fractional changes in blood volume (Hbt) into estimates of changes in blood flow (Grubb et al., 1974) and using the resulting time course to scale the fractional changes in Hbr. The results show an early increase CMRO(2) peaking approximately 2 s after stimulation onset. Using these methods, we find evidence for increased oxygen consumption following increased neural activity even at low levels of stimulation intensity.

Algorithms↗

Spectroscopic analysis of changes in remitted illumination: the response to increased neural activity in brain.

Imaging of neural activation has been used to produce maps of functional architecture and metabolic activity. There is some uncertainty associated with the sources underlying the intrinsic signals. It has been reported that following increased neural activity there was little increased oxygen consumption ( approximately 5%), although glucose consumption increased by approximately 50%. The research we describe uses a modification of the Beer-Lambert Law called path-length scaling analysis (PLSA) to analyze the spectra of the hemodynamic and metabolic responses to vibrissal stimulation in rat somatosensory cortex. The results of the PLSA algorithm were compared with those obtained using a linear spectrographic analysis method (we refer to this as LMCA). There are differences in the results of the analysis depending on which of the two algorithms (PLSA or LMCA) is used. Using the LMCA algorithm, we obtain results showing an increase in the volume of Hbr at approximately 2 s, following onset of stimulation but no complementary decrease in oxygenated haemoglobin (HbO(2)). These results are similar to a previous report. In contrast, after using the PLSA algorithm, the time series of the chromophore changes shows no evidence for an increase in the volume of deoxygenated haemoglobin (Hbr). However, after further analysis of the time series from the PLSA using general linear models (GLM) to remove contributions from low frequency baseline oscillations, both the HbO(2) and Hbr times series of the response to stimulation were found to be biphasic with an early decrease in saturation peaking approximately 1 s after onset of stimulation followed by a larger increase in saturation peaking at approximately 3 s. Finally, following the PLSA-then-GLM analysis procedure, we do not find convincing evidence for an increase in cytochrome oxidation following stimulation, though we demonstrate the PLSA algorithm to be capable of disassociating changes in cytochrome oxidation state from changes in hemoglobin oxygenation.

Algorithms↗

An evaluation of linear model analysis techniques for processing images of microcirculation activity.

Sequences of images of the cortical surface can be processed to reveal information about the cortical microcirculation, regional cerebral blood flow (rCBF), and changes induced by neuronal activity. This study examined the use of different analysis methodologies on intrinsic optical images taken from rat sensory motor cortex and testes. Generalized linear model (GLM) analysis was used and compared with standard signal processing methods including principal component analysis. The GLM method has been used by Friston et al. (1994, Hum. Brain Map., 1: 214-220) in the analysis of functional magnetic resonance imagery to identify regions of focal activity. We investigated the use of this method to analyze video image data of the modulation of rCBF from rat cortex. The results revealed spatiotemporal variations in rCBF in response to stimulation within local regions of cortex. The advantage of the GLM method is that it augments ordinary signal processing methods with an estimate of statistical reliability. The use of different wavelengths of illumination reveals spatial structures with different temporal relationships. In image time series data collected under green and red illumination a phase difference was found in the low frequency approximately 0.1 Hz vasomotion oscillation. This phase difference occurred in data from both cortex and testes. A possible explanation of these differences is that the spectral absorption characteristics of the tissue reflect changes in the volume proportions of the different hemoglobin derivatives in interacting with the modulation of the volume of blood. It is suggested that the combination of these effects produces the phase differences we detect.

Animals↗

Experience with vascular control before excision of giant, highly vascular sacrococcygeal teratomas in neonates.

Sacrococcygeal teratomas (SCT) are the most common neoplasms in newborns with a reported occurrence of 1 in 35,000 live births. Highly vascularized tumors in which the ratio of tumor weight to patient weight approaches 1:1 are frequently associated with hyperdynamic states, prenatal hydrops, placentamegaly, postnatal high-output cardiac failure, and carry a high perinatal mortality rate. Operative management of giant, highly-vascular sacrococcygeal teratomas in neonates can be complicated by life-threatening hemorrhage. Laparotomy, control of the aorta, and the arterial blood supply to these tumors before resection has been advocated as a safer alternative. The authors report their experience with three infants successfully treated using this approach. Hemodynamic stability was maintained during the operations. All tumors were resected successfully. The patients are alive without evidence of recurrence, 8.5 months to 18 months (average, 14.3 months) after the operation. Alpha-fetoprotein levels dropped to normal range after the removal of SCT and have remained normal in follow-up. Vascular control before excision of giant, highly-vascular SCT in neonates is safe, decreases intraoperative blood loss, and postoperative morbidity.

Humans↗

Alcohol risk assessment and intervention for family physicians. Project of the College of Family Physicians of Canada.

At-risk and problem drinkers (excluding those with severe dependency) are estimated to be 20% of the Canadian population. With minimal training family physicians can effectively manage patients with alcohol problems. The Alcohol Risk Assessment and Intervention Project of the College of Family Physicians of Canada has developed materials and training for family physicians to use in helping their patients reduce the risks of alcohol-related harm.

Alcoholism↗