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DALLAS –
“The goal is to have something to guide us, even before we think about applying the McDonald criteria, to give us some probability of whether or not the patient has MS,” Andrew J. Solomon, MD, said at a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
Thalamic atrophy
Measuring thalamic volume is one approach of interest (see Neurol Neuroimmunol Neuroinflamm. 2017 Sep;4[5]:e387). “Thalamic atrophy occurs early in MS,” said Dr. Solomon, division chief of multiple sclerosis in the department of neurological sciences at the University of Vermont, Burlington. “It certainly reflects pathology that seems to be specific to MS, compared to other diseases that mimic MS.”
In a recent analysis, investigators prospectively studied 520 patients with relapse-onset MS and 81 healthy controls who received annual MRI brain scans. MS patients received 2,485 scans during a mean follow-up of 4.1 years, while controls received 147 scans during a mean follow-up of 1.3 years (Ann Neurol. 2018;83[2]:223-34). They found that the annual thalamic volume loss from baseline was significantly greater in MS patients than in controls (–0.71% vs. –0.28%). In addition, lower thalamic volume at baseline correlated modestly with worse baseline disability and functional measures of cognition, ambulation, and upper extremity function.
“Thalamic atrophy can be assessed from clinically acquired 3-D scans,” said Dr. Solomon, who was not involved with the study. “Maybe it can serve as an adjunct for patients who have a low number of lesions for central vein sign evaluation. We can look at their thalamic volume in combination with that and develop a threshold that’s helpful. We need larger cohorts and standardized, automated segmentation.”
Cortical myelin content
Using imaging techniques to detect cortical myelin content also may be beneficial. “We’ve known for a long time that cortical gray matter is involved in MS,” Dr. Solomon said. “It’s really hard to image these lesions on 3T [Tesla] MRI scanners. Some data suggest that patients with migraine don’t have cortical lesions. Patients with neuromyelitis optica don’t seem to have cortical lesions. There is some interesting data using T1 and T2 scans from routine MRI [see Ann Neurol. 2017;82[4]:519-29]. The research suggests that you can develop this ratio and look at myelin content of the cortex.”
Dr. Solomon and his colleagues validated this approach by evaluating data from 20 patients with MS and 10 with migraine. They used the Human Connectome Project pipelines version 3.16.1 to create cortical myelin maps. Specifically, signal intensities from the T1-weighted and FLAIR volumes were used to create maps of ratio and signal intensities as a proxy for cortical myelin content and cortical thickness. Z-score maps were created for each subject, and they used vertices with a Z score of less than 3 as a threshold. They found that the number of vertices in MS vs. non-MS had an area under the curve (AUC) of 0.837. “Maybe looking at cortical myelin content can help us differentiate MS from other disorders,” he said. “It reflects pathology that may be specific to MS. We can use routine clinically acquired sequences. We certainly need much larger cohorts, and we’re working on this.”
Dark rim on gray matter–double inversion recovery
Another promising imaging technique, developed by researchers at the Mayo Clinic, was found to enhance diagnostic specificity in MS (AJNR Am J Neuroradiol. 2018;39[6]:1052-8). Using a novel double inversion recovery sequence that suppresses cerebrospinal fluid and gray matter signal (GM–double inversion recovery), they compared white matter lesions in a group of 107 MS patients and in a second group of 36 positive controls with white matter lesions who did not have a diagnosis of MS. In patients with MS lesions, 35% had a dark rim visible on GM–double inversion recovery, compared with only 1% of the positive control group. Dark rims were associated with a decrease in the lesion T1 ratio. “We need a larger prospective study to see how this pans out,” Dr. Solomon said.
Lesion morphology
Evaluation of lesion morphology also holds promise. In one recent study, researchers performed standardized 3T 3-D brain MRI studies on 19 MS patients and 11 patients with nonspecific white matter (NSWM) disease (J Neuroimaging. 2017;27[6]:613-9). They identified focal supratentorial lesions, used maximum intensity projection to reconstruct them, and created 3-D printed models. The models were randomly evaluated by three blinded raters who scored lesions based on symmetry (symmetrical or asymmetrical), surface morphology (simple or complex), and a long list of secondary characteristics. In all, the researchers evaluated 1,001 supratentorial lesions, including 710 in MS patients and 291 in patients with NSWM disease.
MS vs. NSWM disease lesions had a higher percentage of asymmetry (75.9% vs. 43%; odds ratio, 4.39; P less than .001); complex surface morphologies (65.9% vs. 27.8%; OR, 2.3; P less than .001); multilobular lesions (11% vs. 3%; P less than .001), and elongated lesion (12.8% vs. 2.4%; P less than .001). “This is interesting, but it was a small study,” Dr. Solomon said. “We need to look at this in other diagnoses, and we need prospective data.”
Dr. Solomon disclosed that he has received consulting fees from EMD Serono and research funding from Biogen. He has also performed contracted research for Biogen, Novartis, Actelion, and Genentech/Roche.
dbrunk@mdedge.com
DALLAS –
“The goal is to have something to guide us, even before we think about applying the McDonald criteria, to give us some probability of whether or not the patient has MS,” Andrew J. Solomon, MD, said at a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
Thalamic atrophy
Measuring thalamic volume is one approach of interest (see Neurol Neuroimmunol Neuroinflamm. 2017 Sep;4[5]:e387). “Thalamic atrophy occurs early in MS,” said Dr. Solomon, division chief of multiple sclerosis in the department of neurological sciences at the University of Vermont, Burlington. “It certainly reflects pathology that seems to be specific to MS, compared to other diseases that mimic MS.”
In a recent analysis, investigators prospectively studied 520 patients with relapse-onset MS and 81 healthy controls who received annual MRI brain scans. MS patients received 2,485 scans during a mean follow-up of 4.1 years, while controls received 147 scans during a mean follow-up of 1.3 years (Ann Neurol. 2018;83[2]:223-34). They found that the annual thalamic volume loss from baseline was significantly greater in MS patients than in controls (–0.71% vs. –0.28%). In addition, lower thalamic volume at baseline correlated modestly with worse baseline disability and functional measures of cognition, ambulation, and upper extremity function.
“Thalamic atrophy can be assessed from clinically acquired 3-D scans,” said Dr. Solomon, who was not involved with the study. “Maybe it can serve as an adjunct for patients who have a low number of lesions for central vein sign evaluation. We can look at their thalamic volume in combination with that and develop a threshold that’s helpful. We need larger cohorts and standardized, automated segmentation.”
Cortical myelin content
Using imaging techniques to detect cortical myelin content also may be beneficial. “We’ve known for a long time that cortical gray matter is involved in MS,” Dr. Solomon said. “It’s really hard to image these lesions on 3T [Tesla] MRI scanners. Some data suggest that patients with migraine don’t have cortical lesions. Patients with neuromyelitis optica don’t seem to have cortical lesions. There is some interesting data using T1 and T2 scans from routine MRI [see Ann Neurol. 2017;82[4]:519-29]. The research suggests that you can develop this ratio and look at myelin content of the cortex.”
Dr. Solomon and his colleagues validated this approach by evaluating data from 20 patients with MS and 10 with migraine. They used the Human Connectome Project pipelines version 3.16.1 to create cortical myelin maps. Specifically, signal intensities from the T1-weighted and FLAIR volumes were used to create maps of ratio and signal intensities as a proxy for cortical myelin content and cortical thickness. Z-score maps were created for each subject, and they used vertices with a Z score of less than 3 as a threshold. They found that the number of vertices in MS vs. non-MS had an area under the curve (AUC) of 0.837. “Maybe looking at cortical myelin content can help us differentiate MS from other disorders,” he said. “It reflects pathology that may be specific to MS. We can use routine clinically acquired sequences. We certainly need much larger cohorts, and we’re working on this.”
Dark rim on gray matter–double inversion recovery
Another promising imaging technique, developed by researchers at the Mayo Clinic, was found to enhance diagnostic specificity in MS (AJNR Am J Neuroradiol. 2018;39[6]:1052-8). Using a novel double inversion recovery sequence that suppresses cerebrospinal fluid and gray matter signal (GM–double inversion recovery), they compared white matter lesions in a group of 107 MS patients and in a second group of 36 positive controls with white matter lesions who did not have a diagnosis of MS. In patients with MS lesions, 35% had a dark rim visible on GM–double inversion recovery, compared with only 1% of the positive control group. Dark rims were associated with a decrease in the lesion T1 ratio. “We need a larger prospective study to see how this pans out,” Dr. Solomon said.
Lesion morphology
Evaluation of lesion morphology also holds promise. In one recent study, researchers performed standardized 3T 3-D brain MRI studies on 19 MS patients and 11 patients with nonspecific white matter (NSWM) disease (J Neuroimaging. 2017;27[6]:613-9). They identified focal supratentorial lesions, used maximum intensity projection to reconstruct them, and created 3-D printed models. The models were randomly evaluated by three blinded raters who scored lesions based on symmetry (symmetrical or asymmetrical), surface morphology (simple or complex), and a long list of secondary characteristics. In all, the researchers evaluated 1,001 supratentorial lesions, including 710 in MS patients and 291 in patients with NSWM disease.
MS vs. NSWM disease lesions had a higher percentage of asymmetry (75.9% vs. 43%; odds ratio, 4.39; P less than .001); complex surface morphologies (65.9% vs. 27.8%; OR, 2.3; P less than .001); multilobular lesions (11% vs. 3%; P less than .001), and elongated lesion (12.8% vs. 2.4%; P less than .001). “This is interesting, but it was a small study,” Dr. Solomon said. “We need to look at this in other diagnoses, and we need prospective data.”
Dr. Solomon disclosed that he has received consulting fees from EMD Serono and research funding from Biogen. He has also performed contracted research for Biogen, Novartis, Actelion, and Genentech/Roche.
dbrunk@mdedge.com
DALLAS –
“The goal is to have something to guide us, even before we think about applying the McDonald criteria, to give us some probability of whether or not the patient has MS,” Andrew J. Solomon, MD, said at a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
Thalamic atrophy
Measuring thalamic volume is one approach of interest (see Neurol Neuroimmunol Neuroinflamm. 2017 Sep;4[5]:e387). “Thalamic atrophy occurs early in MS,” said Dr. Solomon, division chief of multiple sclerosis in the department of neurological sciences at the University of Vermont, Burlington. “It certainly reflects pathology that seems to be specific to MS, compared to other diseases that mimic MS.”
In a recent analysis, investigators prospectively studied 520 patients with relapse-onset MS and 81 healthy controls who received annual MRI brain scans. MS patients received 2,485 scans during a mean follow-up of 4.1 years, while controls received 147 scans during a mean follow-up of 1.3 years (Ann Neurol. 2018;83[2]:223-34). They found that the annual thalamic volume loss from baseline was significantly greater in MS patients than in controls (–0.71% vs. –0.28%). In addition, lower thalamic volume at baseline correlated modestly with worse baseline disability and functional measures of cognition, ambulation, and upper extremity function.
“Thalamic atrophy can be assessed from clinically acquired 3-D scans,” said Dr. Solomon, who was not involved with the study. “Maybe it can serve as an adjunct for patients who have a low number of lesions for central vein sign evaluation. We can look at their thalamic volume in combination with that and develop a threshold that’s helpful. We need larger cohorts and standardized, automated segmentation.”
Cortical myelin content
Using imaging techniques to detect cortical myelin content also may be beneficial. “We’ve known for a long time that cortical gray matter is involved in MS,” Dr. Solomon said. “It’s really hard to image these lesions on 3T [Tesla] MRI scanners. Some data suggest that patients with migraine don’t have cortical lesions. Patients with neuromyelitis optica don’t seem to have cortical lesions. There is some interesting data using T1 and T2 scans from routine MRI [see Ann Neurol. 2017;82[4]:519-29]. The research suggests that you can develop this ratio and look at myelin content of the cortex.”
Dr. Solomon and his colleagues validated this approach by evaluating data from 20 patients with MS and 10 with migraine. They used the Human Connectome Project pipelines version 3.16.1 to create cortical myelin maps. Specifically, signal intensities from the T1-weighted and FLAIR volumes were used to create maps of ratio and signal intensities as a proxy for cortical myelin content and cortical thickness. Z-score maps were created for each subject, and they used vertices with a Z score of less than 3 as a threshold. They found that the number of vertices in MS vs. non-MS had an area under the curve (AUC) of 0.837. “Maybe looking at cortical myelin content can help us differentiate MS from other disorders,” he said. “It reflects pathology that may be specific to MS. We can use routine clinically acquired sequences. We certainly need much larger cohorts, and we’re working on this.”
Dark rim on gray matter–double inversion recovery
Another promising imaging technique, developed by researchers at the Mayo Clinic, was found to enhance diagnostic specificity in MS (AJNR Am J Neuroradiol. 2018;39[6]:1052-8). Using a novel double inversion recovery sequence that suppresses cerebrospinal fluid and gray matter signal (GM–double inversion recovery), they compared white matter lesions in a group of 107 MS patients and in a second group of 36 positive controls with white matter lesions who did not have a diagnosis of MS. In patients with MS lesions, 35% had a dark rim visible on GM–double inversion recovery, compared with only 1% of the positive control group. Dark rims were associated with a decrease in the lesion T1 ratio. “We need a larger prospective study to see how this pans out,” Dr. Solomon said.
Lesion morphology
Evaluation of lesion morphology also holds promise. In one recent study, researchers performed standardized 3T 3-D brain MRI studies on 19 MS patients and 11 patients with nonspecific white matter (NSWM) disease (J Neuroimaging. 2017;27[6]:613-9). They identified focal supratentorial lesions, used maximum intensity projection to reconstruct them, and created 3-D printed models. The models were randomly evaluated by three blinded raters who scored lesions based on symmetry (symmetrical or asymmetrical), surface morphology (simple or complex), and a long list of secondary characteristics. In all, the researchers evaluated 1,001 supratentorial lesions, including 710 in MS patients and 291 in patients with NSWM disease.
MS vs. NSWM disease lesions had a higher percentage of asymmetry (75.9% vs. 43%; odds ratio, 4.39; P less than .001); complex surface morphologies (65.9% vs. 27.8%; OR, 2.3; P less than .001); multilobular lesions (11% vs. 3%; P less than .001), and elongated lesion (12.8% vs. 2.4%; P less than .001). “This is interesting, but it was a small study,” Dr. Solomon said. “We need to look at this in other diagnoses, and we need prospective data.”
Dr. Solomon disclosed that he has received consulting fees from EMD Serono and research funding from Biogen. He has also performed contracted research for Biogen, Novartis, Actelion, and Genentech/Roche.
dbrunk@mdedge.com
EXPERT ANALYSIS FROM ACTRIMS FORUM 2019