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Biomedical subjects

Daniel R Altmann

Publications and source records attributed to Daniel R Altmann.

9 recordsLinked to original sources

Quantitative analysis of whole-tumor Gd enhancement histograms predicts malignant transformation in low-grade gliomas.

PURPOSE: To quantify subtle gadolinium (Gd) enhancement (signal increase) in whole-tumor histograms and optimize their ability to predict subsequent malignant transformation in low-grade gliomas (LGGs). MATERIALS AND METHODS: We analyzed histograms from 21 adult subjects with LGGs (eight nontransformers and 13 transformers) who had been imaged every six months for periods of two to five years. Before transformation these tumors were reported as radiologically non-enhancing. Imaging included a T(1)-weighted volume sequence before and after a double dose of Gd-DTPA contrast agent. Image data sets were spatially registered and subtracted to obtain maps of percent enhancement (%E). Tumor outlines were defined on fluid-attenuated inversion recovery (FLAIR) images, and the volumes were calculated. Histogram tails were analyzed to obtain the volume (mL) of subtly enhancing tissue (%E > 10%). RESULTS: Baseline enhancing volumes were higher for Ts than for NTs (P < 0.005). Kaplan-Meier survival curves for a threshold of 4 mL showed clear differences at five years (P < 0.04). Pretransformation examinations predicted transformation (corrected threshold = 3.0 mL, P = 0.011). CONCLUSION: Clear histogram differences at presentation suggest that the process of transformation starts very early. It is now possible to identify individuals at high risk for transformation at baseline by quantifying the volume of subtly enhancing tumor tissue, and such findings could have an impact on patient management.

Adult↗

Principal component and linear discriminant analysis of T1 histograms of white and grey matter in multiple sclerosis.

Twenty-three relapsing remitting multiple sclerosis (RRMS) patients and 14 controls were imaged to produce normal-appearing white and grey matter T1 histograms. These were used to assess whether histogram measures from principal component analysis (PCA) and linear discriminant analysis (LDA) out-perform traditional histogram metrics in classification of T1 histograms into control and RRMS subject groups and in correlation with the expanded disability status score (EDSS). The histograms were classified into one of two groups using a leave-one-out analysis. In addition, the patients were scanned serially, and the calculated parameters correlated with the EDSS. The classification results showed that the more complex techniques were at least as good at classifying the subjects as histogram mean, peak height and peak location, with PCA/LDA having success rates of 76% for white matter and 68%/65% for grey matter. No significant correlations were found with EDSS for any histogram parameter. These results indicate that there is much information contained within the grey matter as well as the white matter histograms. Although in these histograms PCA and LDA did not add greatly to the discriminatory power of traditional histogram parameters, they provide marginally better performance, while relying only on data-driven feature selection.

Brain↗

Adaptive cortical plasticity in higher visual areas after acute optic neuritis.

The ability to distinguish adaptive cortical reorganization may help to target future therapeutic strategies after neurological insult. We investigated cortical plasticity by prospectively applying visual functional magnetic resonance imaging (fMRI) and optic nerve MRI to 20 patients with acute optic neuritis at baseline, 1, 3, 6, and 12 months. We performed three types of correlation analyses to investigate the relationships between fMRI activity, clinical function, and optic nerve structure. The first analysis directly correlated the fMRI response to clinical function or optic nerve structure and found dynamic relations especially within the first 3 months. The second analysis used a novel technique that modeled the fMRI response and optic nerve structure together with clinical function, to determine the contribution fMRI made to clinical function after accounting for structural factors. Significant effects were found at baseline only, within the right peristriate cortex, and bilaterally in the lateral occipital complexes, which are normally involved in higher order visual processing. The third analysis investigated the relation between the modeled visual recovery rate and fMRI response but found no significant effects. The key findings of this study are from the second analysis and suggest a genuine adaptive role for cortical reorganization within extrastriate visual areas early after optic neuritis.

Adaptation, Physiological↗

Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis.

Axonal loss is thought to be a likely cause of persistent disability after a multiple sclerosis relapse; therefore, noninvasive in vivo markers specific for axonal loss are needed. We used optic neuritis as a model of multiple sclerosis relapse to quantify axonal loss of the retinal nerve fiber layer (RNFL) and secondary retinal ganglion cell loss in the macula with optical coherence tomography. We studied 25 patients who had a previous single episode of optic neuritis with a recruitment bias to those with incomplete recovery and 15 control subjects. Optical coherence tomography measurement of RNFL thickness and macular volume, quantitative visual testing, and electrophysiological examination were performed. There were highly significant reductions (p < 0.001) of RNFL thickness and macular volume in affected patient eyes compared with control eyes and clinically unaffected fellow eyes. There were significant relationships among RNFL thickness and visual acuity, visual field, color vision, and visual-evoked potential amplitude. This study has demonstrated functionally relevant changes indicative of axonal loss and retinal ganglion cell loss in the RNFL and macula, respectively, after optic neuritis. This noninvasive RNFL imaging technique could be used in trials of experimental treatments that aim to protect optic nerves from axonal loss.

Adult↗

Serum S100B in primary progressive multiple sclerosis patients treated with interferon-beta-1a.

S100B belongs to a family of calcium-binding proteins implicated in intracellular and extracellular regulatory activities. This study of serum S100B in primary progressive multiple sclerosis (PPMS) is based on data obtained from a randomized, controlled trial of Interferon beta-1a in subjects with PPMS. The key questions were whether S100B levels were associated with either disability or MRI findings in primary progressive MS and whether Interferon beta-1a has an effect on their S100B levels. Serial serum S100B levels were measured using an ELISA method. The results demonstrated that serum S100B is not related to either disease progression or MRI findings in subjects with primary progressive MS given Interferon beta-1a. Furthermore there is no correlation between S100B levels and the primary and secondary outcome measures.

Adult↗

A serial MRI study following optic nerve mean area in acute optic neuritis.

This study assessed optic nerve mean area on serial MRI in a cohort of patients with a first episode of acute unilateral optic neuritis to assess the effects of a single acute inflammatory demyelinating lesion. Twenty-nine patients with a median delay from onset of visual symptoms of 13 days (range 7-24 days) were recruited. After a clinical examination and visual evoked potential (VEP) measurement, each patient had their optic nerves imaged with a coronal fat-saturated short echo fast fluid-attenuated inversion recovery sequence. Twenty-one patients had serial examinations after 2, 4, 8, 12, 26 and 52 weeks. In addition, 32 control subjects had their optic nerves imaged up to three times. The mean cross-sectional area of the intra-orbital portion of each optic nerve was calculated by a blinded observer using a computer-assisted contouring technique. At baseline, the mean area of diseased optic nerves was 16.1 mm2 compared with 13.4 mm2 for healthy contralateral optic nerves (20.1% higher, P < 0.0001) and 13.6 mm2 for controls (18.4% higher, P = 0.0003). The diseased optic nerve mean area declined over time, from initial swelling to later atrophy. The mean decline at 52 weeks was -0.0018 mm2/day (95% confidence interval -0.0038 to -0.00051). At 52 weeks, the mean area of diseased optic nerves was 11.3 mm2 compared with 12.8 mm2 for healthy contralateral optic nerves (11.7% lower, P = 0.032) and 13.1 mm2 for controls (13.7% lower, P = 0.008). The 52 week diseased optic nerve mean area was not significantly affected by the baseline mean area. There was an association between baseline optic nerve mean area and logMAR visual acuity (rS = 0.46, P = 0.012) and visual field mean deviation (rS = -0.55, P = 0.002), but there was no evidence of an association between 1 year mean area and visual outcome. There was no evidence of association between baseline, rates of decline or 1 year diseased optic nerve mean areas and any of the baseline, 1 year or time-averaged VEP variables. The present study shows a consistent pattern of changes associated with individual inflammatory demyelinating lesions in the optic nerve. Acutely, there was swelling, consistent with the presence of acute inflammation, which was related to visual impairment. Over the longer term, there was loss of tissue. The lack of association between 1 year optic nerve mean area and visual outcome may reflect a mild loss of tissue, redundancy or remodelling of function.

Acute Disease↗

Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain.

Several quantitative magnetic resonance (MR) measures are used to investigate multiple sclerosis (MS) in vivo. Precise quantitative investigation of the histopathological correlates of such measures has, to date, been limited. This study investigates the relationship of quantitative measures of myelin content, axonal density, and gliosis with quantitative MR measures in postmortem (PM) MS tissue. MR imaging (MRI) was performed on a 1.5T scanner and T1-relaxation time (T1-RT) and magnetization transfer ratio (MTR) maps were acquired in fresh PM brain of 20 MS subjects. Myelin content, axonal counts, and the extent of gliosis all were quantified using morphometric and digital imaging techniques. MRI and pathological data were in most cases coregistered using stereotactic navigation. Using multiple regression analysis, we detected significant correlations between myelin content (Tr(myelin)) and MTR (r = -0.84, p < 0.001) and myelin content and axonal count (-0.80, p < 0.001); MTR correlated with T1-RT (r = -0.79, p < 0.001). No association was detected between the extent of gliosis and either MR measure. MTR was significantly higher in remyelinated than demyelinated lesions (means: 30.0 [standard deviation, 2.9] vs 23.8 [standard deviation, 4.3], p = 0.008). In conclusion, MTR is affected by myelin content in MS white matter.

Adult↗

Visual recovery following acute optic neuritis--a clinical, electrophysiological and magnetic resonance imaging study.

This study reports the prospective follow-up of a cohort of patients with acute optic neuritis examined with serial visual tests, visual evoked potentials (VEPs), conventional and triple-dose gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) to examine which factors are important in visual recovery. Thirty-three patients were recruited with acute unilateral optic neuritis. A clinical and VEP assessment was performed on each. Optic nerve MRI was performed using fast spin echo (FSE) (on all) and triple-dose Gd-enhanced T1-weighted sequences (n = 28). Optic nerve lesion lengths were measured. Serial assessments were performed on 22 of the patients up to one-year. Serial Gd-enhanced optic nerve imaging was performed on 15 of the patients until enhancement ceased. The final 30-2 Humphrey visual field mean deviation (MD) was 2.55 dB higher in patients in the lowest quartile of initial Gd-enhanced lesion length compared with the other quartiles (p < 0.01) but recovery was not related to the duration of enhancement. The initial recovery of Humphrey MD was 4.60 dB units per day in patients with good eventual recoveries (MD > -6.0 dB) and 0.99 dB per day in poor-recovery patients (p = 0.02).Good-recovery patients had mean central field VEP amplitudes 2.29 microV higher during recovery than poor-recovery patients (p = 0.047). The results suggest that factors which are associated with a better prognosis are: having a short acute lesion on triple-dose gadolinium enhanced imaging, higher VEP amplitudes during recovery and a steep gradient of the initial improvement in vision.

Adult↗

Progressive change in primary progressive multiple sclerosis normal-appearing white matter: a serial diffusion magnetic resonance imaging study.

In spite of marked disability, patients with primary progressive multiple sclerosis (PPMS) display smaller lesion volumes on conventional magnetic resonance imaging (MRI) compared with other forms of multiple sclerosis (MS). Hence, damage to the normal-appearing brain tissue (NABT) may play an important role in explaining the pathogenesis of disability in PPMS. Diffusion-weighted MRI (DW-MRI) probes water diffusion in vivo that can be altered by pathologic changes. Using DW-MRI we investigated diffusion in the NABT of 15 patients with PPMS over one year. The average apparent diffusion coefficient (ADCav) was measured in 10 regions of interest located in the normal-appearing thalamus and the normal-appearing white matter (NAWM). Six healthy subjects served as a reference. In contrast to healthy subjects, patients with PPMS showed an increment within 12 months of the ADCav in NAWM which was associated with an increase of the T2- and T1-lesion volumes. The ADCav in frontal NAWM was associated with disability as measured by the MS Functional Composite Measure. Serial DW-MRI depicts progressive changes in the NAWM of patients with PPMS. Our preliminary findings suggest that the processes causing structural damage in NAWM and lesions in patients with PPMS are partially linked and that changes of water diffusion in NAWM depicted by DW-MRI are clinically relevant.

Adult↗