Treatment outcomes among HIV-positive orphaned and non-orphaned children on antiretroviral therapy in Johannesburg, South Africa.

BACKGROUND: Limited research investigating treatment outcomes for HIV-positive orphans compared with non-orphans has shown mixed results, with several studies indicating that HIV-positive orphans are at greater risk of delayed access to HIV care and poor antiretroviral therapy (ART) adherence, while other data suggest that ART outcomes of orphans can be similar to those of non-orphans. Understanding the impact of orphan status on short-term ART outcomes could improve targeted intervention strategies, and subsequent long-term treatment and developmental outcomes, for HIV-positive infants, children and adolescents. OBJECTIVES: To evaluate the relationship between orphan status and ART outcomes among HIV-positive infants, children and adolescents initiating ART at two large public sector HIV clinics in Johannesburg, South Africa. METHODS: This was a retrospective cohort study of HIV-positive children aged <18 years initiating standard first-line ART between June 2004 and May 2013. Using propensity scores, orphans and non-orphans were matched for age, sex, World Health Organization stage and ART regimen. The effect of orphanhood on attrition from care (all-cause mortality and loss to follow-up) was evaluated using Cox proportional hazards regression analysis, and its effect on having a detectable viral load (≥400 copies/mL) at 12 months on ART using binomial regression analysis with modified Poisson distribution. RESULTS: A total of 251 (29.4%) orphans (maternal, paternal or both) and 603 (70.6%) non-orphans were included at ART initiation. Following multiple imputation for missing data and propensity score matching, 222 orphans and 222 non-orphans were included. Orphans had a median age of 8.0 years (interquartile range (IQR) 4.9 - 10.7) and non-orphans 7.4 years (IQR 4.2 - 10.2). A total of 12 (5.4%) orphans and 33 (14.9%) non-orphans experienced attrition from care during the first 12 months on ART (adjusted hazard ratio 0.32, 95% confidence interval (CI) 0.17 - 0.63). Among those alive and in care, with a viral load at 12 months on ART, 18.0% of orphans (33/183) and 14.8% of non-orphans (24/162) had a detectable viral load (adjusted risk ratio 1.15, 95% CI 1.04 - 1.28). CONCLUSIONS: Orphans were less likely than non-orphans to experience attrition, but among those in care at 12 months, orphans were more likely to have detectable viral loads. Lower attrition among orphans may be due to their being in institutional or foster care, ensuring that they make their visits; however, their higher rates of non-suppression may result from lack of psychosocial support or stigma resulting in struggles to adhere. Additional research investigating age-specific outcomes will be important to elucidate these effects further.

Treatment outcomes among HIV-positive orphaned and non-orphaned children on antiretroviral therapy in Johannesburg, South Africa

Background. Limited research investigating treatment outcomes for HIV-positive orphans compared with non-orphans has shown mixed results, with several studies indicating that HIV-positive orphans are at greater risk of delayed access to HIV care and poor antiretroviral therapy (ART) adherence, while other data suggest that ART outcomes of orphans can be similar to those of non-orphans. Understanding the impact of orphan status on short-term ART outcomes could improve targeted intervention strategies, and subsequent long-term treatment and developmental outcomes, for HIV-positive infants, children and adolescents.Objectives. To evaluate the relationship between orphan status and ART outcomes among HIV-positive infants, children and adolescents initiating ART at two large public sector HIV clinics in Johannesburg, South Africa.Methods. This was a retrospective cohort study of HIV-positive children aged <18 years initiating standard first-line ART between June 2004 and May 2013. Using propensity scores, orphans and non-orphans were matched for age, sex, World Health Organization stage and ART regimen. The effect of orphanhood on attrition from care (all-cause mortality and loss to follow-up) was evaluated using Cox proportional hazards regression analysis, and its effect on having a detectable viral load (≥400 copies/mL) at 12 months on ART using binomial regression analysis with modified Poisson distribution.Results. A total of 251 (29.4%) orphans (maternal, paternal or both) and 603 (70.6%) non-orphans were included at ART initiation. Following multiple imputation for missing data and propensity score matching, 222 orphans and 222 non-orphans were included. Orphans had a median age of 8.0 years (interquartile range (IQR) 4.9 - 10.7) and non-orphans 7.4 years (IQR 4.2 - 10.2). A total of 12 (5.4%) orphans and 33 (14.9%) non-orphans experienced attrition from care during the first 12 months on ART (adjusted hazard ratio 0.32, 95% confidence interval (CI) 0.17 - 0.63). Among those alive and in care, with a viral load at 12 months on ART, 18.0% of orphans (33/183) and 14.8% of non-orphans (24/162) had a detectable viral load (adjusted risk ratio 1.15, 95% CI 1.04 - 1.28).Conclusions. Orphans were less likely than non-orphans to experience attrition, but among those in care at 12 months, orphans were more likely to have detectable viral loads. Lower attrition among orphans may be due to their being in institutional or foster care, ensuring that they make their visits; however, their higher rates of non-suppression may result from lack of psychosocial support or stigma resulting in struggles to adhere. Additional research investigating age-specific outcomes will be important to elucidate these effects further

Relationship between Cough-Associated Changes in CSF Flow and Disease Severity in Chiari I Malformation: An Exploratory Study Using Real-Time MRI.

BACKGROUND AND PURPOSE: Currently no quantitative objective test exists to determine disease severity in a patient with Chiari I malformation. Our aim was to correlate disease severity in symptomatic patients with Chiari I malformation with cough-associated changes in CSF flow as measured with real-time MR imaging. MATERIALS AND METHODS: Thirteen symptomatic patients with Chiari I malformation (tonsillar herniation of ≥5 mm) were prospectively studied. A real-time, flow-sensitized pencil-beam MR imaging scan was used to measure CSF stroke volume during rest and immediately following coughing and relaxation periods (total scan time, 90 seconds). Multiple posterior fossa and craniocervical anatomic measurements were also obtained. Patients were classified into 2 groups by neurosurgeons blinded to MR imaging measurements: 1) nonspecific Chiari I malformation (5/13)-Chiari I malformation with nonspecific symptoms like non-cough-related or mild occasional cough-related headache, neck pain, dizziness, paresthesias, and/or trouble swallowing; 2) specific Chiari I malformation (8/13)-patients with Chiari I malformation with specific symptoms and/or objective findings like severe cough-related headache, myelopathy, syringomyelia, and muscle atrophy. The Spearman correlation was used to determine correlations between MR imaging measurements and disease severity, and both groups were also compared using a Mann-Whitney U test. RESULTS: There was a significant negative correlation between the percentage change in CSF stroke volume (resting to postcoughing) and Chiari I malformation disease severity (R = 0.59; P = .03). Mann-Whitney comparisons showed the percentage change in CSF stroke volume (resting to postcoughing) to be significantly different between patient groups (P = .04). No other CSF flow measurement or anatomic measure was significantly different between the groups. CONCLUSIONS: Our exploratory study suggests that assessment of CSF flow response to a coughing challenge has the potential to become a valuable objective noninvasive test for clinical assessment of disease severity in patients with Chiari I malformation.

Cough-Associated Changes in CSF Flow in Chiari I Malformation Evaluated by Real-Time MRI.

BACKGROUND AND PURPOSE: Invasive pressure studies have suggested that CSF flow across the foramen magnum may transiently decrease after coughing in patients with symptomatic Chiari I malformation. The purpose of this exploratory study was to demonstrate this phenomenon noninvasively by assessing CSF flow response to coughing in symptomatic patients with Chiari I malformation by using MR pencil beam imaging and to compare the response with that in healthy participants. MATERIALS AND METHODS: Eight symptomatic patients with Chiari I malformation and 6 healthy participants were studied by using MR pencil beam imaging with a temporal resolution of ∼50 ms. Patients and healthy participants were scanned for 90 seconds (without cardiac gating) to continuously record cardiac cycle-related CSF flow waveforms in real-time during resting, coughing, and postcoughing periods. CSF flow waveform amplitude, CSF stroke volume, and CSF flow rate (CSF Flow Rate = CSF Stroke Volume × Heart Rate) in the resting and immediate postcoughing periods were determined and compared between patients and healthy participants. RESULTS: There was no significant difference in CSF flow waveform amplitude, CSF stroke volume, and the CSF flow rate between patients with Chiari I malformation and healthy participants during rest. However, immediately after coughing, a significant decrease in CSF flow waveform amplitude (P < .001), CSF stroke volume (P = .001), and CSF flow rate (P = .001) was observed in patients with Chiari I malformation but not in the healthy participants. CONCLUSIONS: Real-time MR imaging noninvasively showed a transient decrease in CSF flow across the foramen magnum after coughing in symptomatic patients with Chiari I malformation, a phenomenon not seen in healthy participants. Our results provide preliminary evidence that the physiology-based imaging method used here has the potential to be an objective clinical test to differentiate symptomatic from asymptomatic patients with Chiari I malformation.

Physiology-based MR imaging assessment of CSF flow at the foramen magnum with a valsalva maneuver.

BACKGROUND AND PURPOSE: MR imaging is currently not used to evaluate CSF flow changes due to short-lasting physiological maneuvers. The purpose of this study was to evaluate the ability of MR imaging to assess the CSF flow response to a Valsalva maneuver in healthy participants. MATERIALS AND METHODS: A cardiac-gated fast cine-PC sequence with ≤15-second acquisition time was used to assess CSF flow in 8 healthy participants at the foramen magnum at rest, during, and immediately after a controlled Valsalva maneuver. CSF mean displacement volume VCSF during the cardiac cycle and CSF flow waveform App were determined. A work-in-progress real-time pencil-beam imaging method with temporal resolution ≤56 ms was used to scan 2 participants for 90 seconds during which resting, Valsalva, and post-Valsalva CSF flow, respiration, and HR were continuously recorded. Results were qualitatively compared with invasive craniospinal differential pressure measurements from the literature. RESULTS: Both methods showed 1) a decrease from baseline in VCSF and App during Valsalva and 2) an increase in VCSF and App immediately after Valsalva compared with values measured both at rest and during Valsalva. Whereas fast cine-PC produced a single CSF flow waveform that is an average over many cardiac cycles, pencil-beam imaging depicted waveforms for each heartbeat and was able to capture many dynamic features of CSF flow, including transients synchronized with the Valsalva maneuver. CONCLUSIONS: Both fast cine-PC and pencil-beam imaging demonstrated expected changes in CSF flow with Valsalva maneuver in healthy participants. The real-time capability of pencil-beam imaging may be necessary to detect Valsalva-related transient CSF flow obstruction in patients with pathologic conditions such as Chiari I malformation.

Cough-associated headache in patients with Chiari I malformation: CSF Flow analysis by means of cine phase-contrast MR imaging.

The purpose of this study was to analyze the CSF flow in patients with Chiari I to determine differences between patients with and without CAH. Thirty patients with Chiari I malformation underwent cine-PC CSF flow imaging in the sagittal plane. CSF flow pulsations were analyzed by placing regions of interest in the anterior cervical subarachnoid space. Maximum CSF systolic (craniocaudal) and diastolic (caudocranial) velocities as well as the durations of CSF systole and diastole (measured in fractions of the cardiac cycle) were determined. In the region of interest just below the foramen magnum, patients with CAH had a significantly shorter CSF systole and longer diastole (P=.02). A CSF diastolic length of ≥0.75 of the cardiac cycle was 67% sensitive and 86% specific for CAH. Our results indicate that Cine-PC imaging can show differences in CSF flow patterns in patients with Chiari I with and without CAH.

25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services.

BACKGROUND: Vitamin D deficiency has potential adverse effects on neurocognitive health and subcortical function. However, no studies have examined the association between vitamin D status, dementia, and cranial MRI indicators of cerebrovascular disease (CVD). METHODS: Cross-sectional investigation of 25-hydroxyvitamin D [25(OH)D], dementia, and MRI measures of CVD in elders receiving home care (aged 65-99 years) from 2003 to 2007. RESULTS: Among 318 participants, the mean age was 73.5 +/- 8.1 years, 231 (72.6%) were women, and 109 (34.3%) were black. 25(OH)D concentrations were deficient (<10 ng/mL) in 14.5% and insufficient (10-20 ng/mL) in 44.3% of participants. There were 76 participants (23.9%) with dementia, 41 of which were classified as probable AD. Mean 25(OH)D concentrations were lower in subjects with dementia (16.8 vs 20.0 ng/mL, p < 0.01). There was a higher prevalence of dementia among participants with 25(OH)D insufficiency (< or =20 ng/mL) (30.5% vs 14.5%, p < 0.01). 25(OH)D deficiency was associated with increased white matter hyperintensity volume (4.9 vs 2.9 mL, p < 0.01), grade (3.0 vs 2.2, p = 0.04), and prevalence of large vessel infarcts (10.1% vs 6.9%, p < 0.01). After adjustment for age, race, sex, body mass index, and education, 25(OH)D insufficiency (< or =20 ng/mL) was associated with more than twice the odds of all-cause dementia (odds ratio [OR] = 2.3, 95% confidence interval [CI] 1.2-4.2), Alzheimer disease (OR = 2.5, 95% CI 1.1-6.1), and stroke (with and without dementia symptoms) (OR = 2.0, 95% CI 1.0-4.0). CONCLUSIONS: Vitamin D insufficiency and deficiency was associated with all-cause dementia, Alzheimer disease, stroke (with and without dementia symptoms), and MRI indicators of cerebrovascular disease. These findings suggest a potential vasculoprotective role of vitamin D.

GABA(C) receptors are expressed in GABAergic and non-GABAergic neurons of the rat superior colliculus and visual cortex.

GABA(C) receptors are enriched in the upper grey layers of the mammalian superior colliculus and contribute to synaptic processing. Electrophysiological data suggested that the GABA(C) receptor ρ subunits are expressed by GABAergic interneurons which represent about half of the neurons in the stratum griseum superficiale (SGS). Combining in situ hybridization for ρ2 receptor mRNA and the glutamic acid decarboxylase GAD-65 mRNA confirmed this assumption. A majority of ρ-labeled neurons in SGS and pretectum are GABAergic. Combining in situ hybridization with immunohistochemistry for the two projection neuron markers calbindin and parvalbumin revealed that a few ρ2 mRNA expressing cells coexpressed calbindin, but not parvalbumin. In visual cortex, ρ2 mRNA was present in pyramidal neurons and parvalbumin-containing interneurons. The results show that in the SGS primarily GABAergic neurons express GABA(C) receptors whereas the majority of tectothalamic calbindin neurons and intrinsically projecting parvalbumin neurons do not.

An open-access, very-low-field MRI system for posture-dependent 3He human lung imaging.

We describe the design and operation of an open-access, very-low-field, magnetic resonance imaging (MRI) system for in vivo hyperpolarized 3He imaging of the human lungs. This system permits the study of lung function in both horizontal and upright postures, a capability with important implications in pulmonary physiology and clinical medicine, including asthma and obesity. The imager uses a bi-planar B(0) coil design that produces an optimized 65 G (6.5 mT) magnetic field for 3He MRI at 210 kHz. Three sets of bi-planar coils produce the x, y, and z magnetic field gradients while providing a 79-cm inter-coil gap for the imaging subject. We use solenoidal Q-spoiled RF coils for operation at low frequencies, and are able to exploit insignificant sample loading to allow for pre-tuning/matching schemes and for accurate pre-calibration of flip angles. We obtain sufficient SNR to acquire 2D 3He images with up to 2.8mm resolution, and present initial 2D and 3D 3He images of human lungs in both supine and upright orientations. 1H MRI can also be performed for diagnostic and calibration reasons.

A System for Open-Access He Human Lung Imaging at Very Low Field.

We describe a prototype system built to allow open-access very-low-field MRI of human lungs using laser-polarized (3)He gas. The system employs an open four-coil electromagnet with an operational B(0) field of 4 mT, and planar gradient coils that generate gradient fields up to 0.18 G/cm in the x and y direction and 0.41 G/cm in the z direction. This system was used to obtain (1)H and (3)He phantom images and supine and upright (3)He images of human lungs. We include discussion on challenges unique to imaging at 50 -200 kHz, including noise filtering and compensation for narrow-bandwidth coils.

3He lung imaging in an open access, very-low-field human magnetic resonance imaging system.

The human lung and its functions are extremely sensitive to gravity; however, the conventional high-field magnets used for most laser-polarized (3)He MRI of the human lung restrict subjects to lying horizontally. Imaging of human lungs using inhaled laser-polarized (3)He gas is demonstrated in an open-access very-low-magnetic-field (<5 mT) MRI instrument. This prototype device employs a simple, low-cost electromagnet, with an open geometry that allows variation of the orientation of the imaging subject in a two-dimensional plane. As a demonstration, two-dimensional lung images were acquired with 4-mm in-plane resolution from a subject in two orientations: lying supine and sitting in a vertical position with one arm raised. Experience with this prototype device will guide optimization of a second-generation very-low-field imager to enable studies of human pulmonary physiology as a function of subject orientation.

The narrow pulse approximation and long length scale determination in xenon gas diffusion NMR studies of model porous media.

We report a systematic study of xenon gas diffusion NMR in simple model porous media, random packs of mono-sized glass beads, and focus on three specific areas peculiar to gas-phase diffusion. These topics are: (i) diffusion of spins on the order of the pore dimensions during the application of the diffusion encoding gradient pulses in a PGSE experiment (breakdown of the narrow pulse approximation and imperfect background gradient cancellation), (ii) the ability to derive long length scale structural information, and (iii) effects of finite sample size. We find that the time-dependent diffusion coefficient, D(t), of the imbibed xenon gas at short diffusion times in small beads is significantly affected by the gas pressure. In particular, as expected, we find smaller deviations between measured D(t) and theoretical predictions as the gas pressure is increased, resulting from reduced diffusion during the application of the gradient pulse. The deviations are then completely removed when water D(t) is observed in the same samples. The use of gas also allows us to probe D(t) over a wide range of length scales and observe the long time asymptotic limit which is proportional to the inverse tortuosity of the sample, as well as the diffusion distance where this limit takes effect (approximately 1-1.5 bead diameters). The Padé approximation can be used as a reference for expected xenon D(t) data between the short and the long time limits, allowing us to explore deviations from the expected behavior at intermediate times as a result of finite sample size effects. Finally, the application of the Padé interpolation between the long and the short time asymptotic limits yields a fitted length scale (the Padé length), which is found to be approximately 0.13b for all bead packs, where b is the bead diameter.

Measuring surface-area-to-volume ratios in soft porous materials using laser-polarized xenon interphase exchange nuclear magnetic resonance.

We demonstrate a minimally invasive nuclear magnetic resonance (NMR) technique that enables determination of the surface-area-to-volume ratio (S/V) of soft porous materials from measurements of the diffusive exchange of laser-polarized 129Xe between gas in the pore space and 129Xe dissolved in the solid phase. We apply this NMR technique to porous polymer samples and find approximate agreement with destructive stereological measurements of S/V obtained with optical confocal microscopy. Potential applications of laser-polarized xenon interphase exchange NMR include measurements of in vivo lung function in humans and characterization of gas chromatography columns.

Tortuosity measurement and the effects of finite pulse widths on xenon gas diffusion NMR studies of porous media.

We have extended the utility of NMR as a technique to probe porous media structure over length scales of approximately 100-2000 microm by using the spin 1/2 noble gas 129Xe imbibed into the system's pore space. Such length scales are much greater than can be probed with NMR diffusion studies of water-saturated porous media. We utilized Pulsed Gradient Spin Echo NMR measurements of the time-dependent diffusion coefficient, D(t), of the xenon gas filling the pore space to study further the measurements of both the pore surface-area-to-volume ratio, S/V(p), and the tortuosity (pore connectivity) of the medium. In uniform-size glass bead packs, we observed D(t) decreasing with increasing t, reaching an observed asymptote of approximately 0.62-0.65D(0), that could be measured over diffusion distances extending over multiple bead diameters. Measurements of D(t)/D(0) at differing gas pressures showed this tortuosity limit was not affected by changing the characteristic diffusion length of the spins during the diffusion encoding gradient pulse. This was not the case at the short time limit, where D(t)/D(0) was noticeably affected by the gas pressure in the sample. Increasing the gas pressure, and hence reducing D(0) and the diffusion during the gradient pulse served to reduce the previously observed deviation of D(t)/D(0) from the S/V(p) relation. The Pade approximation is used to interpolate between the long and short time limits in D(t). While the short time D(t) points lay above the interpolation line in the case of small beads, due to diffusion during the gradient pulse on the order of the pore size, it was also noted that the experimental D(t) data fell below the Pade line in the case of large beads, most likely due to finite size effects.

Analytic reconstruction of magnetic resonance imaging signal obtained from a periodic encoding field.

We have proposed a two-dimensional PERiodic-Linear (PERL) magnetic encoding field geometry B(x,y) = g(y)y cos(q(x)x) and a magnetic resonance imaging pulse sequence which incorporates two fields to image a two-dimensional spin density: a standard linear gradient in the x dimension, and the PERL field. Because of its periodicity, the PERL field produces a signal where the phase of the two dimensions is functionally different. The x dimension is encoded linearly, but the y dimension appears as the argument of a sinusoidal phase term. Thus, the time-domain signal and image spin density are not related by a two-dimensional Fourier transform. They are related by a one-dimensional Fourier transform in the x dimension and a new Bessel function integral transform (the PERL transform) in the y dimension. The inverse of the PERL transform provides a reconstruction algorithm for the y dimension of the spin density from the signal space. To date, the inverse transform has been computed numerically by a Bessel function expansion over its basis functions. This numerical solution used a finite sum to approximate an infinite summation and thus introduced a truncation error. This work analytically determines the basis functions for the PERL transform and incorporates them into the reconstruction algorithm. The improved algorithm is demonstrated by (1) direct comparison between the numerically and analytically computed basis functions, and (2) reconstruction of a known spin density. The new solution for the basis functions also lends proof of the system function for the PERL transform under specific conditions.

Reduced xenon diffusion for quantitative lung study--the role of SF(6).

The large diffusion coefficients of gases result in significant spin motion during the application of gradient pulses that typically last a few milliseconds in most NMR experiments. In restricted environments, such as the lung, this rapid gas diffusion can lead to violations of the narrow pulse approximation, a basic assumption of the standard Stejskal-Tanner NMR method of diffusion measurement. We therefore investigated the effect of a common, biologically inert buffer gas, sulfur hexafluoride (SF(6)), on (129)Xe NMR and diffusion. We found that the contribution of SF(6) to (129)Xe T(1) relaxation in a 1:1 xenon/oxygen mixture is negligible up to 2 bar of SF(6) at standard temperature. We also measured the contribution of SF(6) gas to (129)Xe T(2) relaxation, and found it to scale inversely with pressure, with this contribution approximately equal to 1 s for 1 bar SF(6) pressure and standard temperature. Finally, we found the coefficient of (129)Xe diffusion through SF(6) to be approximately 4.6 x 10(-6) m(2)s(-1) for 1 bar pressure of SF(6) and standard temperature, which is only 1.2 times smaller than the (129)Xe self diffusion coefficient for 1 bar (129)Xe pressure and standard temperature. From these measurements we conclude that SF(6) will not sufficiently reduce (129)Xe diffusion to allow accurate surface-area/volume ratio measurements in human alveoli using time-dependent gas diffusion NMR.

Probing porous media with gas diffusion NMR.

We show that gas diffusion nuclear magnetic resonance (GD-NMR) provides a powerful technique for probing the structure of porous media. In random packs of glass beads, using both laser-polarized and thermally polarized xenon gas, we find that GD-NMR can accurately measure the pore space surface-area-to-volume ratio, S/V rho, and the tortuosity, alpha (the latter quantity being directly related to the system's transport properties). We also show that GD-NMR provides a good measure of the tortuosity of sandstone and complex carbonate rocks.

Line scan diffusion imaging: characterization in healthy subjects and stroke patients.

OBJECTIVE: Our objective was to evaluate a new scanning method, MR line scan diffusion imaging, and assess the apparent diffusion coefficient in the brains of healthy subjects and stroke patients. SUBJECTS AND METHODS: Line scan diffusion imaging without cardiac gating or head restraints was implemented on low- (0.5 T) and medium- (1.5 T) field-strength scanners with conventional hardware. Diffusion-weighted images were obtained in six healthy subjects and eight stroke patients. Unidirectional diffusion encoding was used for fast localization of stroke lesions. For further characterization, orthogonal diffusion encoding was applied, and the trace of the apparent diffusion coefficient was calculated. Single-shot diffusion-weighted echoplanar imaging served as the reference standard. For healthy subjects, imaging was repeated four times on each scanner. Mean and relative precision of the apparent diffusion coefficient trace values were calculated for each pixel. In stroke lesions and adjacent normal tissue, apparent diffusion coefficient trace values were determined. RESULTS: In the 108 scans obtained, line scan diffusion imaging proved to be robust, virtually free of artifact (independent of slice location and orientation), reproducible, and rapid for localization of a stroke. Scan time for 14 slices at 7-mm thickness was 8 min at 0.5 T and 7 min at 1.5 T. Image qualities with line scan diffusion imaging and single-shot diffusion-weighted echoplanar imaging were comparable. At 1.5 T, precision was essentially the same for line scan diffusion imaging (4.3%) and echoplanar imaging (4.7%). With line scan diffusion imaging at 0.5 T and 1.5 T, normal paraventricular apparent diffusion coefficient trace values averaged 0.71 microm2/msec, and with echoplanar imaging these values averaged 0.69 microm2/msec. In acute lesions apparent diffusion coefficient trace values were low, and in chronic lesions these values were high. CONCLUSION: Line scan diffusion imaging on low- and medium-field-strength MR scanners equipped with conventional hardware was reliable and practical for measuring brain apparent diffusion values, which can be applied to the early diagnosis, and hence timely management, of stroke.

Skeletal muscle chemoreflex and pHi in exercise ventilatory control.

To determine whether skeletal muscle hydrogen ion mediates ventilatory drive in humans during exercise, 12 healthy subjects performed three bouts of isotonic submaximal quadriceps exercise on each of 2 days in a 1.5-T magnet for 31P-magnetic resonance spectroscopy (31P-MRS). Bilateral lower extremity positive pressure cuffs were inflated to 45 Torr during exercise (BLPPex) or recovery (BLPPrec) in a randomized order to accentuate a muscle chemoreflex. Simultaneous measurements were made of breath-by-breath expired gases and minute ventilation, arterialized venous blood, and by 31P-MRS of the vastus medialis, acquired from the average of 12 radio-frequency pulses at a repetition time of 2.5 s. With BLPPex, end-exercise minute ventilation was higher (53.3 +/- 3.8 vs. 37.3 +/- 2.2 l/min; P < 0.0001), arterialized PCO2 lower (33 +/- 1 vs. 36 +/- 1 Torr; P = 0.0009), and quadriceps intracellular pH (pHi) more acid (6.44 +/- 0.07 vs. 6.62 +/- 0.07; P = 0.004), compared with BLPPrec. Blood lactate was modestly increased with BLPPex but without a change in arterialized pH. For each subject, pHi was linearly related to minute ventilation during exercise but not to arterialized pH. These data suggest that skeletal muscle hydrogen ion contributes to the exercise ventilatory response.