Toward quantitative neuroimaging biomarkers for Friedreich's ataxia at 7 Tesla: Susceptibility mapping, diffusion imaging, R2 and R1 relaxometry
Friedreich's ataxia (FRDA) is a rare genetic disorder leading to degenerative processes. So far, no effective treatment has been found. Therefore, it is important to assist the development of medication with imaging biomarkers reflecting disease status and progress. Ten FRDA patients (mean age...
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| Veröffentlicht in: | Journal of neuroscience research 2020-11, Vol.98 (11), p.2219-2231 |
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| creator | Straub, Sina Mangesius, Stephanie Emmerich, Julian Indelicato, Elisabetta Nachbauer, Wolfgang Degenhardt, Katja S. Ladd, Mark E. Boesch, Sylvia Gizewski, Elke R. |
| description | Friedreich's ataxia (FRDA) is a rare genetic disorder leading to degenerative processes. So far, no effective treatment has been found. Therefore, it is important to assist the development of medication with imaging biomarkers reflecting disease status and progress. Ten FRDA patients (mean age 37 ± 14 years; four female) and 10 age‐ and sex‐matched controls were included. Acquisition of magnetic resonance imaging (MRI) data for quantitative susceptibility mapping, R1, R2 relaxometry and diffusion imaging was performed at 7 Tesla. Results of volume of interest (VOI)‐based analyses of the quantitative data were compared with a voxel‐based morphometry (VBM) evaluation. Differences between patients and controls were assessed using the analysis of covariance (ANCOVA; p |
| doi_str_mv | 10.1002/jnr.24701 |
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Quantitative 7 Tesla MRI (susceptibility, relaxation, fractional anisotropy) found differences between ten Friedreich's ataxia patients and matched healthy controls in eight structures of brainstem and cerebellum which correlated with disease characteristics. Voxel‐based morphometry revealed white matter atrophy in partially overlapping volumes of interest (VOI) used for the VOI‐based evaluation. *Statistically significant differences between patients and controls; middle cerebellar peduncle (MCP), pontine crossing tract (PCT), corticospinal tract (CS), medial lemniscus (ML), inferior cerebellar peduncle (ICP), superior cerebellar peduncle (SCP), cerebral peduncle (CP), posterior thalamic radiation (PTR), sagittal stratum (SS), dentate nuclei (DN), red nuclei (RN), substantia nigra (SN).</description><identifier>ISSN: 0360-4012</identifier><identifier>EISSN: 1097-4547</identifier><identifier>DOI: 10.1002/jnr.24701</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc</publisher><subject>Age ; Ataxia ; Atrophy ; Biomarkers ; Brain mapping ; Brain stem ; brainstem ; Cerebellum ; Correlation analysis ; Correlation coefficient ; Correlation coefficients ; Covariance ; diffusion imaging ; Evaluation ; fiber tracts ; Friedreich's ataxia ; Genetic disorders ; Magnetic permeability ; Magnetic resonance imaging ; Mapping ; Medical imaging ; midbrain ; Morphometry ; MR relaxometry ; Neuroimaging ; nuclei ; quantitative MRI ; quantitative susceptibility mapping ; Sex ; Statistical analysis ; Statistical significance ; Substantia alba</subject><ispartof>Journal of neuroscience research, 2020-11, Vol.98 (11), p.2219-2231</ispartof><rights>2020 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC</rights><rights>Copyright Wiley Subscription Services, Inc. Nov 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-9167-8778 ; 0000-0003-0217-8630 ; 0000-0001-6859-8377 ; 0000-0001-5870-8472 ; 0000-0001-5790-2724</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjnr.24701$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjnr.24701$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Straub, Sina</creatorcontrib><creatorcontrib>Mangesius, Stephanie</creatorcontrib><creatorcontrib>Emmerich, Julian</creatorcontrib><creatorcontrib>Indelicato, Elisabetta</creatorcontrib><creatorcontrib>Nachbauer, Wolfgang</creatorcontrib><creatorcontrib>Degenhardt, Katja S.</creatorcontrib><creatorcontrib>Ladd, Mark E.</creatorcontrib><creatorcontrib>Boesch, Sylvia</creatorcontrib><creatorcontrib>Gizewski, Elke R.</creatorcontrib><title>Toward quantitative neuroimaging biomarkers for Friedreich's ataxia at 7 Tesla: Susceptibility mapping, diffusion imaging, R2 and R1 relaxometry</title><title>Journal of neuroscience research</title><description>Friedreich's ataxia (FRDA) is a rare genetic disorder leading to degenerative processes. So far, no effective treatment has been found. Therefore, it is important to assist the development of medication with imaging biomarkers reflecting disease status and progress. Ten FRDA patients (mean age 37 ± 14 years; four female) and 10 age‐ and sex‐matched controls were included. Acquisition of magnetic resonance imaging (MRI) data for quantitative susceptibility mapping, R1, R2 relaxometry and diffusion imaging was performed at 7 Tesla. Results of volume of interest (VOI)‐based analyses of the quantitative data were compared with a voxel‐based morphometry (VBM) evaluation. Differences between patients and controls were assessed using the analysis of covariance (ANCOVA; p < 0.01) with age and sex as covariates, effect size of group differences, and correlations with disease characteristics with Spearman correlation coefficient. For the VBM analysis, a statistical threshold of 0.001 for uncorrected and 0.05 for corrected p‐values was used. Statistically significant differences between FRDA patients and controls were found in five out of twelve investigated structures, and statistically significant correlations with disease characteristics were revealed. Moreover, VBM revealed significant white matter atrophy within regions of the brainstem, and the cerebellum. These regions overlapped partially with brain regions for which significant differences between healthy controls and patients were found in the VOI‐based quantitative MRI evaluation. It was shown that two independent analyses provided overlapping results. Moreover, positive results on correlations with disease characteristics were found, indicating that these quantitative MRI parameters could provide more detailed information and assist the search for effective treatments.
Quantitative 7 Tesla MRI (susceptibility, relaxation, fractional anisotropy) found differences between ten Friedreich's ataxia patients and matched healthy controls in eight structures of brainstem and cerebellum which correlated with disease characteristics. Voxel‐based morphometry revealed white matter atrophy in partially overlapping volumes of interest (VOI) used for the VOI‐based evaluation. *Statistically significant differences between patients and controls; middle cerebellar peduncle (MCP), pontine crossing tract (PCT), corticospinal tract (CS), medial lemniscus (ML), inferior cerebellar peduncle (ICP), superior cerebellar peduncle (SCP), cerebral peduncle (CP), posterior thalamic radiation (PTR), sagittal stratum (SS), dentate nuclei (DN), red nuclei (RN), substantia nigra (SN).</description><subject>Age</subject><subject>Ataxia</subject><subject>Atrophy</subject><subject>Biomarkers</subject><subject>Brain mapping</subject><subject>Brain stem</subject><subject>brainstem</subject><subject>Cerebellum</subject><subject>Correlation analysis</subject><subject>Correlation coefficient</subject><subject>Correlation coefficients</subject><subject>Covariance</subject><subject>diffusion imaging</subject><subject>Evaluation</subject><subject>fiber tracts</subject><subject>Friedreich's ataxia</subject><subject>Genetic disorders</subject><subject>Magnetic permeability</subject><subject>Magnetic resonance imaging</subject><subject>Mapping</subject><subject>Medical imaging</subject><subject>midbrain</subject><subject>Morphometry</subject><subject>MR relaxometry</subject><subject>Neuroimaging</subject><subject>nuclei</subject><subject>quantitative MRI</subject><subject>quantitative susceptibility mapping</subject><subject>Sex</subject><subject>Statistical analysis</subject><subject>Statistical significance</subject><subject>Substantia alba</subject><issn>0360-4012</issn><issn>1097-4547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNpdkctu2zAQRYmiBeo6XfQPCGSRLKx4-BBFZRcEcR4wWsB11wIpUikdSZRJKYn_op9c5rHK6s7i4OAOLkI_CJwRALrc9eGM8gLIJzQjUBYZz3nxGc2ACcg4EPoVfYtxBwBlmbMZ-rf1TyoYvJ9UP7pRje7R4t5OwbtO3bv-HmvnOxUebIi48QGvgrMmWFf_PYlYjerZqRS4wFsbW3WOf0-xtsPotGvdeMCdGoZkWWDjmmaKzvf4XbzAG4pVb_CG4GBb9ew7O4bDEfrSqDba7-85R39WV9vLm2z96_r28mKdDRQEyaQgWtR1w0oGmtfUsBwslyYHKeo817VW1EhtrJZMWiFLqqkmErgUktXMsDk6ffMOwe8nG8eqc6l526re-ilWlNOykIIKntDjD-jOT6FP7RLFJQDjhUzU8o16cq09VENIf4ZDRaB6GaZKw1Svw1R3PzevB_sPEfaD7A</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Straub, Sina</creator><creator>Mangesius, Stephanie</creator><creator>Emmerich, Julian</creator><creator>Indelicato, Elisabetta</creator><creator>Nachbauer, Wolfgang</creator><creator>Degenhardt, Katja S.</creator><creator>Ladd, Mark E.</creator><creator>Boesch, Sylvia</creator><creator>Gizewski, Elke R.</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9167-8778</orcidid><orcidid>https://orcid.org/0000-0003-0217-8630</orcidid><orcidid>https://orcid.org/0000-0001-6859-8377</orcidid><orcidid>https://orcid.org/0000-0001-5870-8472</orcidid><orcidid>https://orcid.org/0000-0001-5790-2724</orcidid></search><sort><creationdate>202011</creationdate><title>Toward quantitative neuroimaging biomarkers for Friedreich's ataxia at 7 Tesla: Susceptibility mapping, diffusion imaging, R2 and R1 relaxometry</title><author>Straub, Sina ; 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So far, no effective treatment has been found. Therefore, it is important to assist the development of medication with imaging biomarkers reflecting disease status and progress. Ten FRDA patients (mean age 37 ± 14 years; four female) and 10 age‐ and sex‐matched controls were included. Acquisition of magnetic resonance imaging (MRI) data for quantitative susceptibility mapping, R1, R2 relaxometry and diffusion imaging was performed at 7 Tesla. Results of volume of interest (VOI)‐based analyses of the quantitative data were compared with a voxel‐based morphometry (VBM) evaluation. Differences between patients and controls were assessed using the analysis of covariance (ANCOVA; p < 0.01) with age and sex as covariates, effect size of group differences, and correlations with disease characteristics with Spearman correlation coefficient. For the VBM analysis, a statistical threshold of 0.001 for uncorrected and 0.05 for corrected p‐values was used. Statistically significant differences between FRDA patients and controls were found in five out of twelve investigated structures, and statistically significant correlations with disease characteristics were revealed. Moreover, VBM revealed significant white matter atrophy within regions of the brainstem, and the cerebellum. These regions overlapped partially with brain regions for which significant differences between healthy controls and patients were found in the VOI‐based quantitative MRI evaluation. It was shown that two independent analyses provided overlapping results. Moreover, positive results on correlations with disease characteristics were found, indicating that these quantitative MRI parameters could provide more detailed information and assist the search for effective treatments.
Quantitative 7 Tesla MRI (susceptibility, relaxation, fractional anisotropy) found differences between ten Friedreich's ataxia patients and matched healthy controls in eight structures of brainstem and cerebellum which correlated with disease characteristics. Voxel‐based morphometry revealed white matter atrophy in partially overlapping volumes of interest (VOI) used for the VOI‐based evaluation. *Statistically significant differences between patients and controls; middle cerebellar peduncle (MCP), pontine crossing tract (PCT), corticospinal tract (CS), medial lemniscus (ML), inferior cerebellar peduncle (ICP), superior cerebellar peduncle (SCP), cerebral peduncle (CP), posterior thalamic radiation (PTR), sagittal stratum (SS), dentate nuclei (DN), red nuclei (RN), substantia nigra (SN).</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/jnr.24701</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-9167-8778</orcidid><orcidid>https://orcid.org/0000-0003-0217-8630</orcidid><orcidid>https://orcid.org/0000-0001-6859-8377</orcidid><orcidid>https://orcid.org/0000-0001-5870-8472</orcidid><orcidid>https://orcid.org/0000-0001-5790-2724</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Ataxia Atrophy Biomarkers Brain mapping Brain stem brainstem Cerebellum Correlation analysis Correlation coefficient Correlation coefficients Covariance diffusion imaging Evaluation fiber tracts Friedreich's ataxia Genetic disorders Magnetic permeability Magnetic resonance imaging Mapping Medical imaging midbrain Morphometry MR relaxometry Neuroimaging nuclei quantitative MRI quantitative susceptibility mapping Sex Statistical analysis Statistical significance Substantia alba |
| title | Toward quantitative neuroimaging biomarkers for Friedreich's ataxia at 7 Tesla: Susceptibility mapping, diffusion imaging, R2 and R1 relaxometry |
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