Proton T2 relaxation of cerebral metabolites of normal human brain over large TE range.

T2 of NAA, creatine and choline-containing compounds were measured in posterior frontal white matter and occipital grey matter in 10 healthy human volunteers. Decay curves comprised signals from eight TE times ranging from 30 to 800 ms with TR 2000 ms acquired with a PRESS sequence on a 1.5 T clinical scanner. Simulations were conducted to assess the precision of T2 estimates from decay curves comprising varying numbers and ranges of TE points. Mean and standard errors for T2s of NAA, creatine and choline-containing compounds were 300(8), 169(3) and 239(4) ms in posterior frontal white matter and 256(6), 159(8) and 249(8) ms in occipital grey matter. In vivo T2s found for choline and NAA were shorter than the T2s in the literature. The elevation of literature T2s is accounted for by the simulation results, which demonstrated that there is a bias towards lengthened T2s when T2 is measured with a maximum TE approximately T2. Concentration estimates are at risk of being underestimated if previously reported T2 corrections are used.

Heterogeneity of narrowing in normal and asthmatic airways measured by HRCT.

Asthmatic airway narrowing is heterogeneous and contributes to airway hyperresponsiveness. The present study compared heterogeneity of narrowing during methacholine challenge in asthmatics and normal subjects using high-resolution computed tomography (HRCT). The current authors defined heterogeneity as variability in narrowing greater than the repeatability of measurement. Airways of <2 mm diameter were compared with larger airways from baseline and postmethacholine HRCT of the right lower lung in 13 normals (seven had repeat baseline scans) and seven asthmatics. The coefficient of repeatability was calculated from repeat scans (RepAi) and was compared with heterogeneity of narrowing measured by the variability in narrowing from pre versus postmethacholine scans (VardeltaAi). Forced expiratory volume in one second decreased 27+/-6% and 24+/-8% in normals and asthmatics, respectively. Airways >2 mm narrowed more heterogeneously in asthmatics (VardeltaAi=+/-0.85 mm) compared with normals (VardeltaAi=+/-0.67 mm), with both being greater than the measure of repeatability (RepAi=+/-0.16 mm). Small airway narrowing was not heterogeneous in asthmatics (VardeltaAi=+/-0.59 mm) or normals (VardeltaAi=+/-0.53 mm) compared with repeatability (RepAi=0.51 mm). It is possible to study heterogeneity of airway narrowing in small and large airways using high resolution computed tomography. Airway narrowing is heterogeneous in the large airways of asthmatics and normals, being greater in asthmatics.

Proton T1 relaxation times of cerebral metabolites differ within and between regions of normal human brain.

Saturation recovery spectra (STEAM) were acquired at 1.5 T with 7 TRs ranging from 530 to 5000 ms and a constant TE of 30 ms in voxels (7.2 ml) located in occipital grey, parietal white and frontal white matter (10 subjects each location). Spectra were also acquired at 7, 21 and 37 degrees C from separate 100 mm solutions of inositol (Ins), choline-containing compounds (Cho), N-acetyl-aspartate (NAA) and creatine. Simulations of T(1) fits with 2, 3 and 7 TRs demonstrated that at typical SNR there is potential for both inaccurate and biased results. In vivo, different metabolites had significantly different T(1)s within the same brain volume. The same order from shortest to longest T(1) (Ins, Cho, NAA, creatine) was found for all three brain regions. The order (Ins, NAA, creatine, Cho) was found in the metabolite solutions and was consistent with a simple model in which T(1) is inversely proportional to molecular weight. For all individual metabolites, T(1) increased from occipital grey to parietal white to frontal white matter. This study demonstrates that, in spectra acquired with TR near 1 s, T(1) weightings are substantially different for metabolites within a single tissue and also for the same metabolites in different tissues.

Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins.

Schizophrenia unfolds during the late period of brain maturation, while myelination is still continuing. In the present study, we used MRI and T2 relaxation analysis to measure the myelin water fraction in schizophrenia. In schizophrenia (n=30) compared with healthy subjects (n=27), overall white matter showed 12% lower myelin water fraction (P=0.031), with the most prominent effects on the left genu of the corpus callosum (36% lower, P=0.002). The left anterior genu was affected in both first-episode (P=0.035) and chronic patients (P=0.011). In healthy subjects, myelin water fraction in total white matter and in frontal white matter increased with age, and with years of education, indicating ongoing maturation. In patients with schizophrenia, neither relation was statistically significant. Post-mortem studies of anterior frontal cortex demonstrated less immunoreactivity of two oligodendrocyte-associated proteins in schizophrenia (2',3'-cyclic nucleotide 3'-phosphodiesterase by 33%, P=0.05; myelin-associated glycoprotein by 27%, P=0.14). Impaired myelination in schizophrenia could contribute to abnormalities of neural connectivity and persistent functional impairment in the illness.

Selection of patients for lung volume reduction surgery using a power law analysis of the computed tomographic scan.

BACKGROUND: A study was undertaken to test the hypothesis that patients respond better to lung volume reduction surgery (LVRS) if their emphysema is confluent and predominantly located in the upper lobes. METHODS: A density mask analysis was used to identify voxels inflated beyond 10.2 ml gas/g tissue (-910 HU) on preoperative and postoperative CT scans from patients receiving LVRS. These hyperinflated regions were considered to represent emphysematous lesions. A power law analysis was used to determine the relationship between the number (K) and size (A) of the emphysematous lesions in the whole lung and two anatomical regions using the power law equation Y=KA(-D). RESULTS: The analysis showed a positive correlation between the change in the power law exponent (D) and the change in exercise (Watts) after surgery (r=0.47, p=0.03). There was also a negative correlation between the power law exponent D in the upper region of the lung preoperatively and the change in exercise following surgery (r=-0.60, p<0.05). CONCLUSIONS: These results confirm that patients with large upper lobe lesions respond better to LVRS than patients with small uniformly distributed disease. Power law analysis of lung CT scans provides a quantitative method for determining the extent and location of emphysema within the lungs of patients with COPD.

Muscle cross-sectional area is associated with specific site of bone in prepubertal girls: a quantitative magnetic resonance imaging study.

It is well established that forces applied to bone are the result of muscle contraction. However, data regarding the contribution of muscle cross-sectional area (because muscle area is proportional to muscle strength) to cortical bone area before puberty are controversial. We tested the hypothesis that muscle cross-sectional area is associated with total cortical bone area, and whether there is a region-specific relationship between these parameters in prepubertal and early pubertal girls. Seventeen healthy (9-11 years, Tanner stages I-II) white girls participated in the study. We measured bone loading characteristics (maximal ground reaction forces; GRFs) for a drop jump (50 cm) and side-to-side jump (over a 20-cm-high fence) on a multicomponent force platform. Muscle cross-sectional area and bone cortical area (square centimeters) of the proximal third of the left and right lower leg was measured with a 1.5 T magnetic resonance system using a quadrature head coil. The sequence was T(1) weighted, with spin-echo in transverse (tibial) planes and 3 mm sections with no gap (ten slices). The tibial cross-sectional areas were subdivided into three anatomical sectors (SI-SIII), with the tibial centroid as origin. SI extended from the medial tibial border to the most anterior edge, SII extended from the anterior edge laterally to the interosseous border, and SIII extended posteromedially from the interosseous border to the medial tibial border. The nonparametric bone and muscle volume correlations demonstrated that the total muscle cross-sectional area correlated significantly with the total cortical area in both legs (left leg: r(s) = 0.59, p = 0.020; right leg: r(s) = 0.57, p = 0.016). Significant correlations were also found between left and right muscle area and cortical area in SII (r(s) = 0.68, p = 0.003, 0.67, and 0.003, respectively). There was no significant association between the muscle area and cortical area in SI or SIII. In addition, there was a significant correlation between GRFs of the side-to-side jump and total cortical area (left leg: r = 0.75, p < 0.01; right leg: r = 0.78, p < 0.01). Thus, we found that muscle area was most highly associated with bone cortical area in SII, the anterolateral sector of the tibia, which emphasizes the specific interplay of muscles and bone in the lower limb. This relationship was present in a regional, site-specific fashion.

Different magnetization transfer effects exhibited by the short and long T(2) components in human brain.

Magnetization transfer ratios (MTRs) were measured separately for the two T(2) components in white matter. For both binomial and off-resonance sinc MT pulses, the MTR was larger for the short T(2) component than for the long T(2) component. This differential MT effect disappeared for delays between the MT pulse and the multi-echo pulse sequence longer than 200 msec, indicating exchange between the two components. When using the sinc MT pulse, the MTR for the short T(2) component was similar for different white matter structures, whereas it varied for different white matter structures when using the binomial pulse-a phenomenon attributed to direct saturation. When the sinc pulse frequency was brought closer to resonance, MTRs in white matter and doped water phantoms increased for both components but more so for the shorter T(2) component. This behavior was consistent with a Bloch equation model of direct saturation.

A pathology-MRI study of the short-T2 component in formalin-fixed multiple sclerosis brain.

OBJECTIVE: To determine the pathologic basis of areas not exhibiting signal of the short-T2 component of the T2 relaxation distribution in MS, as studied in formalin-fixed brain. BACKGROUND: A myelin-specific MRI signal would be of great importance in assessing demyelination in patients with MS. Evidence indicates that the short-T2 (10 to 50 millisecond) component of the T2 relaxation distribution originates from water in myelin sheaths. The authors present two cases of MS in which the anatomic distribution of the short-T2 component was correlated with the pathologic findings in postmortem formalin-fixed brain. METHOD: One half of the formalin-fixed brain was suspended in a gelatin-albumin mixture cross-linked with glutaraldehyde, and scanned with a 32-echo MRI sequence. The brain was then cut along the center of the 5-mm slices scanned, photographed, dehydrated, and embedded in paraffin. Paraffin sections, stained with Luxol fast blue and immunocytochemically for 2',3'-cyclic nucleotide 3'-phosphohydrolase for myelin and by the Bielschowsky technique for axons, were compared with the distribution of the amplitude of the short-T2 component of the comparable image slices. RESULTS: The anatomic distribution of the short-T2 component signal corresponded to the myelin distribution. Chronic, silent MS plaques with myelin loss correlated with areas of absence of short-T2 signal. The numbers of axons within lesions were reduced, but many surviving axons were also seen in these areas of complete loss of myelin. CONCLUSION: In formalin-fixed MS brains the short-T2 component of the T2 relaxation distribution corresponds to the anatomic distribution of myelin. Chronic, silent demyelinated MS plaques show absence of the short-T2 component signal. These results support the hypothesis that the short-T2 component originates from water related to myelin.-1510

Preoperative severity of emphysema predictive of improvement after lung volume reduction surgery: use of CT morphometry.

STUDY OBJECTIVE: To determine how the volume and severity of emphysema measured by CT morphometry (CTM) before and after lung volume reduction surgery (LVRS) relates to the functional status of patients after LVRS. DESIGN: A histologically validated CT algorithm was used to quantify the volume and severity of emphysema in 35 patients before and after LVRS: total lung volume (TLV), normal lung volume (< 6.0 mL gas per gram of tissue), volume of mild/moderate emphysema (ME; 6.0 to 10.2 mL gas per gram of tissue), volume of severe emphysema (> 10.2 mL gas per gram of tissue), surface area/volume (SA/V; meters squared per milliliter), and surface area (SA; meters squared). Outcome parameters included maximal cardiopulmonary exercise (CPX) performance in 21 patients and routine pulmonary function in all patients. We hypothesized that baseline CTM parameters predict response to LVRS and that the change in these parameters may offer insight into mechanisms of improvement. PATIENTS AND INTERVENTION: Thirty-five patients with severe emphysema who had successful LVRS. RESULTS: The significant decrease in TLV following LVRS was entirely accounted for by a decrease in severe emphysema. The SA/V and the SA both increased significantly following LVRS. The change in maximal CPX in watts following surgery correlated significantly with baseline values of severe emphysema (r = 0.60), which was collinear with TLV, and SA/V. The change in diffusing capacity of the lung for carbon monoxide revealed a significant positive linear relationship with preoperative severe emphysema (r = 0.37) and a negative relationship with ME (r = -0.37). Change in watts revealed a strong relationship with changes in severe emphysema (r = -0.75) and weaker but significant relationships with change in TLV, ME, SA/V, and SA. Other measures of pulmonary function revealed significant albeit less dominant relationships with baseline CTM and change in these indexes. CONCLUSION: Using CTM, we have identified a close relationship between baseline severe emphysema, or change in severe emphysema, and the improvement in CPX after LVRS. These observations support a potential role of CTM in future clinical trials for predicting responders to LVRS and identifying mechanisms of improvement.

An analysis algorithm for measuring airway lumen and wall areas from high-resolution computed tomographic data.

High-resolution computed tomography (HRCT) has been used to examine airway narrowing. We developed an automated computed tomographic image analysis algorithm (computed tomographic airway morphometry; CTAM) to measure airway lumen area (Ai ), airway wall area (Awa), and airway angle of orientation. Tubes of varying size were embedded in Styrofoam and then scanned at angles between 0 degrees and 50 degrees to assess the accuracy of measurements made with CTAM. Two excised pig lungs were fixed in inflation, sectioned, and scanned. Ai and Awa were measured planimetrically from the cut surfaces to optimize CTAM measurement parameters. In CTAM, Ai was defined according to an airway-size-dependent threshold value, and total Awa was determined through a score-guided erosion method. Results were compared with measurements made through a previously validated method (manual method). CTAM provided accurate measurements of the tubes' Ai values at all angles; Awa was overestimated in direct relation to airway size. The manual method underestimated Ai and overestimated Awa in a manner directly related to airway size as well as to airway angle of orientation. In the excised lung, the mean errors of Ai and Awa measurements made with CTAM were 0.52 +/- 0.24 mm(2) and 0.17 +/- 0.32 mm(2) (mean +/- SEM), respectively. Ai errors with the manual method were similar, but Awa was overestimated to a greater degree (6.3 +/- 0.38 mm(2); p < 0.01) and the error was proportional to Awa (r = 0.64; p < 0.01). CTAM allows accurate measurements of airway dimensions and angle of orientation.

A model of unloaded human intervertebral disk based on NMR relaxation.

NMR relaxation rates were related to the composition of the nucleus pulposus from 11 and anulus fibrosus from six human intervertebral disks. Tissue water was proportional to glycosaminoglycan (GAG) and residue, the noncollagen, non-GAG portion of the dry weight (R2 = 0.74). The solid signal fraction depended on collagen and residue protons (R2 = 0.89). 1/T1 was proportional to collagen and residue (R2 = 0.97). T2 showed 2-4 components labeled A, B, C, and D, with means +/- standard deviations of 3.1 +/- 1.6, 17.5 +/- 9.5, 64 +/- 22, and 347 +/- 162 msec. Signal fractions of A and B depended on the collagen-associated water protons (R2 = 0.94 and 0.85), C on residue-associated water protons (R2 = 0.82), and D on GAG-associated water protons (R2 = 0.74). The data led to a model of disk architecture in which the collagen and residue were largely solid, forming distinct water compartments; the remaining water was present in a proteoglycan gel.

Are mono-exponential fits to a few echoes sufficient to determine T2 relaxation for in vivo human brain?

T2 relaxation decay curves from in vivo human brain tissue are rarely mono-exponential. Partial volume averaging further reduces the chance of mono-exponential decay. Moreover, the parameters derived from few-echo mono-exponential fits change with the measurement echo times and have the largest possible variance. In this note, multi-exponential fits to 32-echo relaxation decay curves from in vivo human brain are used to design simulations (where the truth is known) to demonstrate the pitfalls of few-echo mono-exponential interpretations.

A quantification of the lung surface area in emphysema using computed tomography.

Quantitative analysis of computed tomography (CT) has been combined with a stereologically based histologic analysis of lung structure to assess regional lung inflation and the structural features of the lung parenchyma. In this study, CT measurements of lung inflation were compared with histologic estimates of surface area in order to develop prediction equations that allow lung surface to volume ratio and surface area to be predicted from an analysis of the CT scan. The results show that mild emphysema is associated with an increase in lung volume and a reduction in surface to volume ratio, whereas surface area and tissue weight were only decreased in severe disease. The CT predicted surface to volume ratio correlated with histology, and both predicted and measured surface areas correlated with the diffusing capacity. We conclude that this CT analysis can be used to monitor the progression of emphysematous lung destruction in individual patients, and to assess the impact of both surgical and medical treatments for emphysema.

Functional magnetic resonance imaging: the basics of blood-oxygen-level dependent (BOLD) imaging.

There are 2 principal techniques of functional MRI (fMRI): the blood-oxygen-level dependent (BOLD) technique, which is the favoured method because no intravenous contrast medium is required, and the dynamic or exogenous technique. The BOLD technique takes advantage of the fact that the change from diamagnetic oxyhemoglobin to paramagnetic deoxyhemoglobin that takes place with brain activation results in decreased signal intensity on MRI. Commercially available scanners can be used to conduct single-slice BOLD fMRI experiments, but echo-planar hardware is needed for multislice wholebrain experiments. Sequence choices in BOLD fMRI include spin-echo and gradient-echo sequences, to which rapid acquisition with relaxation enhancement and echoplanar techniques may be applied. Optimal imaging parameters (echo time, slice thickness, field of view and flip angle) are important in maximizing signal-to-noise ratios. Various statistical techniques and software programs have been developed to interpret the large amounts of data gathered from BOLD fMRI experiments, which presents one of the biggest challenges in performing this technique with clinical MR units. Controversy exists regarding the effects of draining veins on cortical mapping, of inflow of blood into the imaging slice or volume, and of motion artifact. BOLD fMRI has demonstrated good correlation with positron emission tomography, magneto-encephalography and electrocorticographic recordings of motor responses. It has been used to study cortical activity of visual, motor, auditory and speech tasks as well as brain centres for smell, motor imagery, complex motion and memory. As such, it holds promise for the study of brain function, but must be subjected to larger studies comparing it with the gold standard of electrocorticographic mapping.

A comparison between magnetization transfer ratios and myelin water percentages in normals and multiple sclerosis patients.

Magnetization transfer and T2 relaxation data were obtained for five white and six gray matter brain structures from 10 normal volunteers and 9 multiple sclerosis patients. Thirty MS lesions were also analyzed. Magnetization transfer ratios and myelin water percentages were compared. Both techniques showed a significant difference between the average of white and gray matter of the normal volunteers as well as the average of normal-appearing white matter and gray matter of the multiple sclerosis patients. The average magnetization transfer ratio and myelin water percentage for lesions were significantly lower than those of normal-appearing white matter. Myelin water percentages and magnetization transfer ratios were uncorrelated in white and gray matter but showed a small (R = 0.5, P = 0.005) but significant correlation in multiple sclerosis lesions. In summary, the myelin water percentage and the magnetization transfer ratio provide quantifiable but largely independent measures of multiple sclerosis lesion pathology.

CT-based analysis of the geometry of the distal femur.

When applying minimally invasive techniques (MIO, Minimally Invasive Osteosynthesis) to the fixation of the distal femur, the surgeon has access to a limited number of anatomical landmarks: namely the articular surface of the distal femur and a small portion of the distal lateral femoral cortex. A detailed knowledge of the local anatomy facilitates the technique and prevents complications. Using Kirschner wires placed at set positions in the distal femur, we analyzed the measurements obtained from the 3D reconstructed helical CT scans of 33 embalmed femora and we report on the anatomy of the distal femur as it relates to supracondylar fracture fixation.

Quantification of idiopathic pulmonary fibrosis using computed tomography and histology.

We used computed tomography (CT) and histologic analysis to quantify lung structure in idiopathic pulmonary fibrosis (IPF). CT scans were obtained from IPF and control patients and lung volumes were estimated from measurements of voxel size, and X-ray attenuation values of each voxel. Quantitative estimates of lung structure were obtained from biopsies obtained from diseased and normal CT regions using stereologic methods. CT density was used to calculate the proportion of tissue and air, and this value was used to correct the biopsy specimens to the level of inflation during the CT scan. The data show that IPF is associated with a reduction in airspace volume with no change in tissue volume or weight compared with control lungs. Lung surface area decreased two-thirds (p < 0.001) and mean parenchymal thickness increased tenfold (p < 0.001). An exudate of fluid and cells was present in the airspace of the diseased lung regions and the number of inflammatory cells, collagen, and proteoglycans was increased per 100 g of tissue in IPF. We conclude that IPF reorganized lung tissue content causing a loss of airspace and surface area without increasing the total lung tissue.

Simulated dose reduction in conventional chest CT: validation study.

PURPOSE: To validate a technique of computer-simulated dose reduction for conventional chest computed tomography (CT). MATERIALS AND METHODS: In 27 patients, CT scans were obtained at 200, 100, and 40 mAs at two levels. The raw data from the 200-mAs scan were modified on a computer workstation to simulate the increased noise present on 100- and 40-mAs scans. Real and simulated 100- and 40-mAs images were independently assessed in random order for overall image quality and radiologic findings by four subspecialty-trained chest radiologists who were blinded to the technique. The four observers were given paired real and simulated images. They were asked to identify the real image and note any difference in diagnostic quality. RESULTS: No difference was seen in overall image quality or radiologic findings between real and simulated images (P > .05). In the paired comparison, 433 of 864 (50.1%) real images were correctly identified. CONCLUSION: Computer modification of 200-mAs raw scan data to simulate 100- and 40-mAs noise levels produces reconstructed images indistinguishable from real 100- and 40-mAs scans. This technique provides realistic reduced-dose images without patient radiation exposure and with identical image registration and motion artifact.