Řádek 13:Buffalo Neuroimaging Analysis Center, State University of New York X Department of Radiology of the 1st Faculty of Medicine and General University Hospital in Prague
- Relevance of the strategy
This staff mobility will allow us expansionof our magnetic resonance imaging (MRI) possibilitiesfor the investigationof patientswith multiple sclerosis (MS). Our MScenteris the largest one in the Central Europeand cooperation with one of the leading US centers further strengthen our position in Europe.
Proposedmobility projectconcernsinterconnection, data sharing, creatinginternational standardsfor monitoringmagnetic resonance imaging (MRI) in patientswith multiple sclerosis (MS).Our partner will be the Buffalo Neuroimaging Analysis Center, State University of New York. It isone of the leadingUSdepartmentsengaged in the researchof multiple sclerosis. Our MR unit has collaborated with Buffalo Neuroimaging Analysis Center, State University of New York since 2006. List of numerous joint publications is enclosed.. Suggested cooperativeworkwill cover theissueof MRIvolumometry
We would like to validate the MRI methodology used in our MR unit in the Czech Republic and compare with the measurements used in the Buffalo imaging center. We would like personally discuss the measurement of the volume of the thalamus, used in their workplace. In Prague we have developer fundaments of the monitoring technique - quantitative MRI (Q-MRI), which monitors both pathological processes occuring at MS- inflammation and neurodegeneration. This monitoring was implemented into practice in the Czech Republic. However, the program has not been validated yet at other locations. Validation of MRI measurements for different environments, implementation of the clinic and supplement the methodology for linking to Buffalo imaging center is therefore the main goal of this mobility project.The results of this cooperationwe would like to share with other university departments throughout Europe and the USA
- Quality of the cooperation arrangements
Charles University in Prague, First Faculty of Medicine, Department of Radiology, MR unit, has collaborated with Buffalo Neuroimaging Analysis Center, State University of New York since 2006.
Quality of collaboration directly follows from this joint publication list;
Horakova D, Dwyer MG, Havrdova E, Cox JL, Dolezal O, Bergsland N, Rimes B, Seidl Z, Vaneckova M, Zivadinov R. Gray matter atrophy and disability progression in patients with early relapsing-g multiple sclerosis. A 5-year longitudinal study. J Neurol Sci. 2009 Jul 15;282(1-2):112-9.
Bergsland N, Horakova D, Dwyer MG, Dolezal O, Seidl Z, Vaneckova M, Krasensky J, Havrdova E, Zivadinov R. Subcortical and cortical gray matter atrophy in a large sample of patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol. 2012 Sep;33(8):1573-8 (IF 3,167)
Zivadinov R, Havrdova E, Bergsland N, Tyblova M, Hagemeire J, Seidl Z, Dwyer MG, Vaneckova M, Krasensky J, Carl E, Kalincik T, Horakova D. ThalamicAtrophyIsAssociatedwithDevelopmentofClinicalDefiniteMultipleSclerosis. Radiology 2013 2013 Sep;268(3):831-841.
Weinstock-Guttman B, Zivadinov R, Horakova D, Havrdova E, Qu J, Shyh G, Lakota E, O'Connor K, Badgett D, Tamaño-Blanco M, Tyblova M, Hussein S, Bergsland N, Willis L, Krasensky J, Vaneckova M, Seidl Z, Ramanathan M. Lipid profiles are associatedwithlesionformationover 24 months in interferon-β treatedpatientsfollowingthefirstdemyelinating event. J NeurolNeurosurg Psychiatry. 2013 Apr 17.
Browne RW, Weinstock-Guttman B, Horakova D, Zivadinov R, Bodziak ML, Tamaño-Blanco M, Badgett D, Tyblova M, Vaneckova M, Seidl Z, Krasensky J, Bergsland N, Ramasamy DP, Hagemeier J, Havrdova E, Ramanathan M. Apolipoproteins are Associatedwith New MRI Lesions and DeepGrayMatterAtrophy in ClinicallyIsolatedSyndromes. JNNP 2014, Aug 85(8):859-64.
Severalcolleagues from Department of Neurology in Praguehave already worked onthe cooperatingworkplace.It broughtto ourworkplaceknowledge whichwehave also utilizedin our research. It broughtvery close cooperation. This visit of Prof. Manuela Vaneckova should be the first visit from the Radiology department.
We collaboratedonresearchregarding the presenceof corticalbearings inMSpatients.We have shownbeforethe adventof more sophisticatedmethodsfor detectingpathologiesof the gray matter, thecortexis affectedfrom the beginning ofthe diseaseand the numberof bearingsincreases withdisease duration. We further foundthat thecorticalbearingsbettercorrelatewith clinicaldisabilitythanhypersignalbearingsT2Wimage.
We dealt within cooperationwith theBuffalowithenvironmental factorsrelated toMSand biochemicalmarkers inRSandtheir relationshipto the bearingdisabilitiesmagnetic resonance. We found an increasing evidence that serum lipoprotein cholesterol
biomarkers are associated with disease progression in clinically isolated
syndromes (CIS). The objective of another study was to investigate whether serum Apo levels are associated with CIS disease progression.
- Quality of project design and implementation
A mutualbilateral cooperation has been already set;we share the data and we both test the evaluating systems.Ourcommon goalis to create theMRmonitoringschemefor worldwide use.
In collaboration with the State University of New York in Buffalo, NY, USA we will be measuring the central gray matter, we will compare measurements of atrophy of the thalamus, the lateral ventricles and corpus callosum. The aim of this research is to identify the most robust markers and determine whether they are independent of each other and whether their merger will result in even higher predictive power.
Multiple sclerosis (MS) is a chronic disorder of the nervous system with highly variable and unpredictable clinical course. We currently have no cure for MS, however, with the help of timely anti-inflammatory therapy we are able to ameliorate its course. Efficacy of the available treatments in individual patients is highly variable. Therefore the exact quantification of disease activity is crucial. For this purpose, the currently available clinical variables (relapses and EDSS) and conventional MRI markers (number of lesions) are of a limited value. Volumetric MRI (global and regional brain atrophy) seems to be better predictor of continuing clinical activity.
The aims of the project are:
1)to identify quantitative MRI markers with improved individual descriptive and predictive values
2)to implement quantitative measurement of brain volume change into a real clinical practice
Project: Multicenter study will be designed in two phases: the retrospective and prospective one. The retrospective part of the study will use already collected data from 150 MS patients at three different sites (Buffalo, Prague and Sydney). The following MRI measures will be generated:
- Percentage change in whole brain volume
- Percentage change in gray matter (GM) volume
- Percentage change in lateral ventricle volume (LVV)
- Number of new/enlarging T2 lesions
- Absolute T2-lesion volume and absolute change in T2-lesion volume
The use of different software methods and approaches to the same data set will validate sensitivity and specificity in detecting changes over time. The data will be also assessed by exploring relationship between different software methods and approaches with clinical outcomes. The QMRI and radiological reports will be compared in a blinded manner.
In addition, a prospective part of the study will include 150 MS patients at three different sites (Buffalo, Prague and Sydney). The inclusion criteria for that part of the study will be:
- Being relapsing-remitting (RR=25) or secondary-progressive (SP=25) MS patient at each site
- Having baseline MRI scan acquired using standardized MRI protocol at 1.5T or 3T in which there is a presence of high resolution 3D-T1 and 2D or 3D FLAIR sequence
- Obtaining a follow-up MRI standardized MRI scan at the same scanner in real time separated at least one or more years apart from the baseline scan
- Having Expanded Disability Status Scale (EDSS) assessment at baseline and at follow-up
- Not having steroid treatment or relapse 30 days prior to the MRI scan at baseline or follow-up
- Having radiological examination by a certified MRI reader
- Obtaining a clinical questionnaire in which the treating/examining neurologist evaluates usefulness of QMRI report in real time for individual MS patient decision making. In particular the questionnaire will focus on: establishing or ruling out a diagnosis of MS; starting or changing DMT; determining prognosis; establishing which quantitative MRI metric is the most helpful in clinical decision making; and comparing the information with radiological qualitative MRI evaluation alone.
At each site the scans will be analyzed by the local imaging center and by the icoMetrix centrally.
Correlation between the icoMetrix measures and the local image analysis reports (for all atrophy and lesion measures): a Pearson correlation analysis as well as measurement of the intra-class correlation coefficient (ICC)
A logistic regression analysis will be performed to evaluate the role of the different MRI measures in predicting clinical changes.
From the radiological reports, a % of reports will be calculated that contains quantitative information on either brain atrophy and/or lesion count and changes. For the reports that contain quantitative information, a regression analysis will be used to correlate these outcomes with the MRI measures derived by image analysis.
For the prospective analyses, a similar comparison between the methods as well as correlation with clinical outcome will be performed. In addition, a clinical questionnaire will be created for every patient by the local treating clinician. Based on these questionnaires, the value and clinical utility of the different MRI reports will be compared and they will be used to further improve the use of quantitative MRI information and QMRI reports in clinical practice.
- Impact and dissemination
The project seeksto spread technique of theMRvolumometrytouniversity facilities all over the world.
The projectshould help usextend ourresultsoutside theCzechRepublic, in the Europe, wherewe are oneof themain centersdealing withvolumometryin MS patients. The projectis of great practicalimpact, because it showsthatMRis the mainbiomarker thathelps to findappropriate treatmentfor an individual patientwith MS.The predictiveability ofMRshows how thediseaseirreversiblyproceeds; it wouldbetimelyto electadequate treatment.
The goal of project is to evaluate the use QMRI report and establish its value, as a new standardized instrument for assessment of disease activity and clinical progression on a routine basis for individual patients with MS. Among the MRI measures, part of the QMRI report, we will evaluate change in global and tissue specific brain atrophy measures, accumulation of new/enlarging lesions and progression of lesion volume in clinical decision making.
The project aimsfirst to compare themeasurement techniquesonboth sites, with the aimto findthe most robustmarkerin terms oflong-termpredictionsof disease progression. Checkwhetherthe methodologydevelopedforMRunitisalso applicable toother academicwork. Whether thetransmission systemanddata sharingbetweenradiologicaland clinicalworkplaces(MSCenter,NeurologicalClinic) is user-friendlyenoughto quickenandespeciallyimprove the quality ofcare for patients withMS.
MRmonitoringcould thenbecome a leadingparameter forthe treatment algorithmMSpatients.MRimportanceinthe last few yearshas increased significantlysince they were introducedin practicethenew therapeuticdrugs.