An oblique cylinder contrast-adjusted (OCCA) phantom to measure the accuracy of MRI brain lesion volume estimation schemes in multiple sclerosis

A new OCCA phantom using Oblique Cylinders and Contrast Adjustment for measuring the accuracy of brain lesion volume estimation schemes is described. It uses obliquely oriented cylinders made from acrylic rod, mounted in a water bath, to give realistic partial volume errors. Image intensities are inverted, scaled, and shifted, and noise is added, to form images that have realistic values of lesion-white matter contrast (5-30%) and contrast-to-noise ratio (3-20%). Artificial gray matter, CSF (cerebrospinal fluid), and scalp lipid are added because these bright areas may determine how the gray level display window is set. The performance of manual and contouring methods for estimating lesion volume was measured for three observers and nine lesions with individual volumes from 0.3 to 6.2 ml. There was a large variation, depending on the choice of method, the observer, and the lesion contrast. Volumes were usually overestimated, with the error increasing at high contrasts. The average error in estimating total lesion volume was 17% (range -16% to +30%). The OCCA phantom may have a role in training observers to improve their accuracy (and hence inter- and intraobserver reproducibility)

Antibodies to islet 37k antigen, but not to glutamate decarboxylase, discriminate rapid progression to IDDM in endocrine autoimmunity

Apart from islet cell antibodies (ICAs), antibodies to glutamate decarboxylase (GAD), insulin autoantibodies (IAAs), and a novel islet antigen (37k antigen) are potential markers for insulin-dependent diabetes mellitus (IDDM). GAD is also an antigen in stiff-man syndrome (SMS), and both SMS and IDDM are associated with ICAs and autoimmunity to other endocrine organs. We investigated possible links between antibody responses to islet antigens with autoimmunity to other endocrine organs and determined which specific antibodies can identify individuals who progress to IDDM. Antibodies to GAD were detected in â?¥90 of both diabetic and nondiabetic patients with ICAs and other endocrine autoimmunity, in 59 of ICA-positive IDDM patients without endocrine autoimmunity, in all patients with SMS, but in only 1-3 of healthy (nondiabetic) and autoimmune disease control subjects. GAD antibody levels were increased in ICA-positive IDDM patients with polyendocrine autoimmunity compared with those without. In contrast, antibodies to 37k antigen were only detected in patients who developed acute-onset IDDM. IAAs were also associated with IDDM. Thus, certain factors enhance antibody responses to GAD in polyendocrine autoimmunity, but this does not necessarily lead to development of IDDM or SMS. Antibodies to 37k antigen are strongly associated with acute-onset IDDM and are useful serological markers for disease.</p

Antibodies to islet 37k antigen, but not to glutamate decarboxylase, discriminate rapid progression to IDDM in endocrine autoimmunity

Apart from islet cell antibodies (ICAs), antibodies to glutamate decarboxylase (GAD), insulin autoantibodies (IAAs), and a novel islet antigen (37k antigen) are potential markers for insulin-dependent diabetes mellitus (IDDM). GAD is also an antigen in stiff-man syndrome (SMS), and both SMS and IDDM are associated with ICAs and autoimmunity to other endocrine organs. We investigated possible links between antibody responses to islet antigens with autoimmunity to other endocrine organs and determined which specific antibodies can identify individuals who progress to IDDM. Antibodies to GAD were detected in â?¥90 of both diabetic and nondiabetic patients with ICAs and other endocrine autoimmunity, in 59 of ICA-positive IDDM patients without endocrine autoimmunity, in all patients with SMS, but in only 1-3 of healthy (nondiabetic) and autoimmune disease control subjects. GAD antibody levels were increased in ICA-positive IDDM patients with polyendocrine autoimmunity compared with those without. In contrast, antibodies to 37k antigen were only detected in patients who developed acute-onset IDDM. IAAs were also associated with IDDM. Thus, certain factors enhance antibody responses to GAD in polyendocrine autoimmunity, but this does not necessarily lead to development of IDDM or SMS. Antibodies to 37k antigen are strongly associated with acute-onset IDDM and are useful serological markers for disease.</p

Correlation of magnetic resonance imaging parameters with clinical disability in multiple sclerosis: a preliminary study

Magnetic resonance imaging (MRI) is frequently used to monitor new treatments in multiple sclerosis (MS), but its role is limited by the uncertain relationship between MRI parameters and clinical disability. A brain MRI study using nine MRI parameters was undertaken in 15 MS patients with a wide spectrum of disability to evaluate the relationship between each parameter and disability. A strong correlation was found between disability (measured using Kurtzke's EDSS) and total lesion load on both proton density (PD; r = 0.79) and T1 (r = 0.71) weighted sequences. There was also a strong correlation of disability with average lesion magnetisation transfer ratio (MTR; r = -0.74) and calculated T1 (r = 0.71) but not with calculated T2 or the average signal intensity of lesions on the conventional T1-weighted, PD-weighted and heavily T2-weighted images. Thus, four parameters which measured either the extent of lesions (PD lesion load) or their pathological severity (MTR, calculated T1, hypointense T1-lesion load) were correlated significantly with disability. While this suggests that such parameters will be useful in treatment trial monitoring, further multi-parameter MRI studies, of larger cohorts and using a wider range of techniques, are indicated

Correlation of magnetic resonance imaging parameters with clinical disability in multiple sclerosis: a preliminary study

Magnetic resonance imaging (MRI) is frequently used to monitor new treatments in multiple sclerosis (MS), but its role is limited by the uncertain relationship between MRI parameters and clinical disability. A brain MRI study using nine MRI parameters was undertaken in 15 MS patients with a wide spectrum of disability to evaluate the relationship between each parameter and disability. A strong correlation was found between disability (measured using Kurtzke's EDSS) and total lesion load on both proton density (PD; r = 0.79) and T1 (r = 0.71) weighted sequences. There was also a strong correlation of disability with average lesion magnetisation transfer ratio (MTR; r = -0.74) and calculated T1 (r = 0.71) but not with calculated T2 or the average signal intensity of lesions on the conventional T1-weighted, PD-weighted and heavily T2-weighted images. Thus, four parameters which measured either the extent of lesions (PD lesion load) or their pathological severity (MTR, calculated T1, hypointense T1-lesion load) were correlated significantly with disability. While this suggests that such parameters will be useful in treatment trial monitoring, further multi-parameter MRI studies, of larger cohorts and using a wider range of techniques, are indicated