Contributions
Abstract: P474
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Brain Volume Loss (BVL) is increasingly considered a component of the assessment of brain health in individuals with Multiple Sclerosis (MS). The next frontier is to translate BVL measurements into clinical practice and individual patient care. To appraise BVL measurements, clinicians need to know what to expect from their individualized MS patients, relative to gender and age. This will further provide clinical usefulness of BVL in individualized MS patient care.
Goal: To establish a normative cross-sectional and longitudinal Brain Volume reference range.
Methods: A model was developed from a reference population of 1213 subjects with multiple observation points (total of 3665 MRIs). BVL was assessed by Brain Parenchymal Fraction (BPF) using an in-house method based on the segmentation of combined T2 and PD. The model adjusts for repeated measurements on each patient and estimates the effect of age, gender and disease duration on a patient"s baseline BPF in addition to the rate of change in each patient"s BPF over time. The model estimates the level of variation associated with BPF measurements both within and between patients.
Results: Age, gender and disease duration at baseline each had a significant impact on BPF. Female BPF is 2.6% larger than Male BPF on average given the same age and disease duration. A 10 year increase in age is associated with a 1% decrease in BPF on average. A 10 year increase in duration is associated with a 2% decrease in BPF on average. Subjects showed a consistent decrease in BPF over time. Using age or disease duration give similar results in our model. Disease duration is often difficult to determine, so age is more reliable.
Based on the model, the BPF of a typical patient can be predicted given their gender, age and disease duration. By predicting the BPF at different times, the typical change in BPF can also be predicted. The level of variation estimated by the model is used to provide a range of plausible values for each prediction.
Conclusion: By modeling a large population of MS patients, we can provide a meaningful context in which clinicians can interpret BVL in an individualized patient, both in term of brain volume (BPF) at one point in time and of BVL(ΔBPF) between two different assessments. It can determine brain volume trajectory in individual patients. Real world usefulness of Brain Volume Loss measurements is still to be determined. Our model is a stepping-stone toward this ultimate goal.
Disclosure:
Philippe Beauchemin: Consulting fees: Novartis, EMD Serono.
Robert Carruthers: Grants/Research Support: Site PI for studies funded by MedImmune, Teva and Guthy Jackson; Speakers Bureau/Honoraria: Speaking fees for unbranded lectures from Biogen, Genzyme and Teva; Consulting Fees: Novartis, EMD Serono, Genzyme.
Roger Tam: nothing to disclose.
Andrew Riddehough: nothing to disclose.
David Li: has received research funding from the Canadian Institute of Health Research and Multiple Sclerosis Society of Canada. He is the Director of the UBC MS/MRI Research Group which has been contracted to perform central analysis of MRI scans for therapeutic trials with Novartis, Perceptives, Roche and Sanofi-Aventis. The UBC MS/MRI Research Group has also received grant support for investigator-initiated independent studies from Genzyme, Merck-Serono, Novartis and Roche. He has acted as a consultant to Vertex Pharmaceuticals and served on the Data and Safety Advisory Board for Opexa Therapeutics and Scientific Advisory Boards for Adelphi Group, Novartis and Roche. He has also given lectures which have been supported by non-restricted education grants from Novartis and Biogen.
Rick White: nothing to disclose.
Anthony Traboulsee: is a consultant for Novartis, Genzyme, Roche and a principal investigator on clinical trials with Biogen, Genzyme, Roche, and Chugai.
Abstract: P474
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Brain Volume Loss (BVL) is increasingly considered a component of the assessment of brain health in individuals with Multiple Sclerosis (MS). The next frontier is to translate BVL measurements into clinical practice and individual patient care. To appraise BVL measurements, clinicians need to know what to expect from their individualized MS patients, relative to gender and age. This will further provide clinical usefulness of BVL in individualized MS patient care.
Goal: To establish a normative cross-sectional and longitudinal Brain Volume reference range.
Methods: A model was developed from a reference population of 1213 subjects with multiple observation points (total of 3665 MRIs). BVL was assessed by Brain Parenchymal Fraction (BPF) using an in-house method based on the segmentation of combined T2 and PD. The model adjusts for repeated measurements on each patient and estimates the effect of age, gender and disease duration on a patient"s baseline BPF in addition to the rate of change in each patient"s BPF over time. The model estimates the level of variation associated with BPF measurements both within and between patients.
Results: Age, gender and disease duration at baseline each had a significant impact on BPF. Female BPF is 2.6% larger than Male BPF on average given the same age and disease duration. A 10 year increase in age is associated with a 1% decrease in BPF on average. A 10 year increase in duration is associated with a 2% decrease in BPF on average. Subjects showed a consistent decrease in BPF over time. Using age or disease duration give similar results in our model. Disease duration is often difficult to determine, so age is more reliable.
Based on the model, the BPF of a typical patient can be predicted given their gender, age and disease duration. By predicting the BPF at different times, the typical change in BPF can also be predicted. The level of variation estimated by the model is used to provide a range of plausible values for each prediction.
Conclusion: By modeling a large population of MS patients, we can provide a meaningful context in which clinicians can interpret BVL in an individualized patient, both in term of brain volume (BPF) at one point in time and of BVL(ΔBPF) between two different assessments. It can determine brain volume trajectory in individual patients. Real world usefulness of Brain Volume Loss measurements is still to be determined. Our model is a stepping-stone toward this ultimate goal.
Disclosure:
Philippe Beauchemin: Consulting fees: Novartis, EMD Serono.
Robert Carruthers: Grants/Research Support: Site PI for studies funded by MedImmune, Teva and Guthy Jackson; Speakers Bureau/Honoraria: Speaking fees for unbranded lectures from Biogen, Genzyme and Teva; Consulting Fees: Novartis, EMD Serono, Genzyme.
Roger Tam: nothing to disclose.
Andrew Riddehough: nothing to disclose.
David Li: has received research funding from the Canadian Institute of Health Research and Multiple Sclerosis Society of Canada. He is the Director of the UBC MS/MRI Research Group which has been contracted to perform central analysis of MRI scans for therapeutic trials with Novartis, Perceptives, Roche and Sanofi-Aventis. The UBC MS/MRI Research Group has also received grant support for investigator-initiated independent studies from Genzyme, Merck-Serono, Novartis and Roche. He has acted as a consultant to Vertex Pharmaceuticals and served on the Data and Safety Advisory Board for Opexa Therapeutics and Scientific Advisory Boards for Adelphi Group, Novartis and Roche. He has also given lectures which have been supported by non-restricted education grants from Novartis and Biogen.
Rick White: nothing to disclose.
Anthony Traboulsee: is a consultant for Novartis, Genzyme, Roche and a principal investigator on clinical trials with Biogen, Genzyme, Roche, and Chugai.