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  • Bendszus, Martin  (10)
  • Kollmer, Jennifer  (10)
  • 1
    In: European Journal of Neurology, Wiley, Vol. 29, No. 6 ( 2022-06), p. 1782-1790
    Abstract: Knowledge about the exact underlying pathophysiological changes involved in the genesis and progression of spinocerebellar ataxia type 3 (SCA3) is limited. Lower extremity peripheral nerve lesions in clinically, genetically and electrophysiologically classified ataxic and pre‐ataxic SCA3 mutation carriers were characterized and quantified by magnetic resonance neurography (MRN). Methods Eighteen SCA3 mutation carriers and 20 age‐/sex‐matched healthy controls were prospectively enrolled. All SCA3 mutation carriers underwent detailed neurological and electrophysiological examinations. 3 T MRN covered the lumbosacral plexus and proximal thigh to the tibiotalar joint by using T2‐weighted inversion recovery sequences, dual‐echo relaxometry sequences with spectral fat saturation, and two gradient‐echo sequences with and without an off‐resonance saturation rapid frequency pulse. Detailed quantification of nerve lesions by morphometric and microstructural MRN markers, including T2 relaxometry and magnetization transfer contrast imaging, was conducted in all study participants. Results MRN detected peripheral nerve damage in ataxic and pre‐ataxic SCA3. The quantitative markers proton spin density ( ρ ), T2 relaxation time, magnetization transfer ratio and cross‐sectional area were decreased in SCA3, indicating chronic axonopathy. MTR and ρ identified early, subclinical nerve damage in pre‐ataxic SCA3 and in SCA3 mutation carriers without polyneuropathy and were superior in differentiating between all subgroups. Additionally, microstructural markers correlated well with clinical symptom scores and electrophysiological results. Conclusions Our data provide a comprehensive characterization of peripheral nerve damage in SCA3 and assist in understanding the mechanisms of the multisystemic disease evolution. Evidence of peripheral nerve involvement prior to the onset of clinically overt ataxia might have important implications for designing early intervention studies.
    Type of Medium: Online Resource
    ISSN: 1351-5101 , 1468-1331
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2020241-6
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  • 2
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 93, No. 7 ( 2019-08-13), p. e653-e664
    Abstract: To characterize and quantify peripheral nerve lesions and muscle degeneration in clinically, genetically, and electrophysiologically well-classified, nonpediatric patients with 5q-linked spinal muscular atrophy (SMA) by high-resolution magnetic resonance neurography (MRN). Methods Thirty-one adult patients with genetically confirmed 5q-linked SMA types II, IIIa, and IIIb and 31 age- and sex-matched healthy volunteers were prospectively investigated. All patients received neurologic, physiotherapeutic, and electrophysiologic assessments. MRN at 3.0T with anatomic coverage from the lumbosacral plexus and proximal thigh down to the tibiotalar joint was performed with dual-echo 2D relaxometry sequences with spectral fat saturation and a 3D T2-weighted inversion recovery sequence. Detailed quantification of nerve injury by morphometric and microstructural MRN markers and qualitative classification of fatty muscle degeneration were conducted. Results Established clinical scores and compound muscle action potentials discriminated well between the 3 SMA types. MRN revealed that peroneal and tibial nerve cross-sectional area (CSA) at the thigh and lower leg level as well as spinal nerve CSA were markedly decreased throughout all 3 groups, indicating severe generalized peripheral nerve atrophy. While peroneal and tibial nerve T2 relaxation time was distinctly increased at all analyzed anatomic regions, the proton spin density was clearly decreased. Marked differences in fatty muscle degeneration were found between the 3 groups and for all analyzed compartments. Conclusions MRN detects and quantifies peripheral nerve involvement in SMA types II, IIIa, and IIIb with high sensitivity in vivo. Quantitative MRN parameters (T2 relaxation time , proton spin density, CSA) might serve as novel imaging biomarkers in SMA to indicate early microstructural nerve tissue changes in response to treatment.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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  • 3
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 89, No. 5 ( 2017-08-01), p. 475-484
    Abstract: To detect and quantify lesions of the small-caliber sural nerve (SN) in symptomatic and asymptomatic transthyretin familial amyloid polyneuropathy (TTR-FAP) by high-resolution magnetic resonance neurography (MRN) in correlation with electrophysiologic and histopathologic findings. Methods: Twenty-five patients with TTR-FAP, 10 asymptomatic carriers of the mutated transthyretin gene (mut TTR ), and 35 age- and sex-matched healthy controls were prospectively included in this cross-sectional case-control study. All participants underwent 3T MRN with high-structural resolution (fat-saturated, T2-weighted, and double-echo sequences). Total imaging time was ≈45 minutes per patient. Manual SN segmentation was performed from its origin at the sciatic nerve bifurcation to the lower leg with subsequent evaluation of quantitative microstructural and morphometric parameters. Additional time needed for postprocessing was ≈1.5 hours per participant. Detailed neurologic and electrophysiologic examinations were conducted in the TTR group. Results: T2 signal and proton spin density (ρ) reliably differentiated between TTR-FAP (198.0 ± 13.3, 429.6 ± 15.25), mut TTR carriers (137.0 ± 16.9, p = 0.0009; 354.7 ± 21.64, p = 0.0029), and healthy controls (90.0 ± 3.4, 258.2 ± 9.10; p 〈 0.0001). Marked differences between mut TTR carriers and controls were found for T2 signal ( p = 0.0065) and ρ ( p 〈 0.0001). T2 relaxation time was higher in patients with TTR-FAP only ( p = 0.015 vs mut TTR carriers, p = 0.0432 vs controls). SN caliber was higher in patients with TTR-FAP vs controls and in mut TTR carriers vs controls ( p 〈 0.0001). Amyloid deposits were histopathologically detectable in 10 of 14 SN specimens. Conclusions: SN injury in TTR-FAP is detectable and quantifiable in vivo by MRN even in asymptomatic mut TTR carriers. Differences in SN T2 signal between controls and asymptomatic mut TTR carriers are derived mainly from an increase of ρ, which overcomes typical limitations of established diagnostic methods as a highly sensitive imaging biomarker for early detection of peripheral nerve lesions. Classification of evidence: This study provides Class III evidence that MRN accurately identifies asymptomatic mut TTR carriers.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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  • 4
    In: Annals of Neurology, Wiley, Vol. 78, No. 6 ( 2015-12), p. 939-948
    Abstract: The aim of this work was to localize and quantify alterations of nerve microstructure in diabetic polyneuropathy (DPN) by magnetic resonance (MR) neurography with large anatomical coverage. Methods Patients (N = 25) with mild‐to‐moderate (Neuropathy‐Symptom‐Score [NSS]/Neuropathy Deficit Score [NDS] 3.8 ± 0.3/2.6 ± 0.5) and patients (n = 10) with severe DPN (6.2 ± 0.6/7.4 ± 0.5) were compared to patients (n = 15) with diabetes but no DPN and to age‐/sex‐matched nondiabetic controls (n = 25). All subjects underwent MR neurography with large spatial coverage and high resolution from spinal nerve to ankle level: four slabs per leg, each with 35 axial slices (T2‐ and proton‐density–weighted two dimensional turbo‐spin‐echo sequences; voxel size: 0.4 × 0.3 × 3.5 mm 3 ) and a three‐dimensional T2‐weighted sequence to cover spinal nerves and plexus. Nerve segmentation was performed on a total of 280 slices per subject. Nerve lesion voxels were determined independently from operator input by statistical classification against the nondiabetic cohort. At the site with highest lesion‐voxel burden, signal quantification was performed by calculating nerve proton spin density and T2 relaxation time. Results Total burden of nerve lesion voxels was significantly increased in DPN ( p  = 0.003) with strong spatial predominance at thigh level, where average lesion voxel load was significantly higher in severe (57 ± 18.4; p  = 0.0022) and in mild‐to‐moderate DPN (35 ± 4.0; p   〈  0.001) than in controls (18 ± 3.6). Signal quantification at the site of predominant lesion burden (thigh) revealed a significant increase of nerve proton spin density in severe (360 ± 22.9; p  = 0.043) and in mild‐to‐moderate DPN (365 ± 15.2; p  = 0.001) versus controls (288 ± 13.4), but not of T2 relaxation time ( p  = 0.49). Nerve proton spin density predicted severity of DPN with an odds ratio of 2.9 (95% confidence interval: 2.4–3.5; p   〈  0.001) per 100 proton spins. Interpretation In DPN, the predominant site of microstructural nerve alteration is at the thigh level with a strong proximal‐to‐distal gradient. Nerve proton spin density at the thigh level is a novel quantitative imaging biomarker of early DPN and increases with neuropathy severity. Ann Neurol 2015;78:939–948
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2037912-2
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  • 5
    In: Annals of Neurology, Wiley, Vol. 82, No. 5 ( 2017-11), p. 676-685
    Abstract: To detect and quantify peripheral nerve lesions in multiple sclerosis (MS) by magnetic resonance neurography (MRN). Methods Thirty‐six patients diagnosed with MS based on the 2010 McDonald criteria (34 with the relapsing–remitting form, 2 with clinically isolated syndrome) with and without disease‐modifying treatment were compared to 35 healthy age‐/sex‐matched volunteers. All patients underwent detailed neurological and electrophysiological examinations. Three Tesla MRN with large anatomical coverage of both legs and the lumbosacral plexus was performed by using 2‐dimensional (2D) fat‐saturated, T2‐weighted (T2w) and dual echo turbo spin echo sequences as well as a 3D T2‐weighted, fat‐saturated SPACE sequence. Besides qualitative visual nerve assessment, a T2w signal quantification was performed by calculation of proton spin density and T2 relaxation time. Nerve diameter was measured as a morphometric criterion. Results T2w hyperintense nerve lesions were detectable in all MS patients, with a mean lesion number at thigh level of 151.5 ± 5.7 versus 19.1 ± 2.4 in controls ( p   〈  0.0001). Nerve proton spin density was higher in MS (tibial/peroneal: 371.8 ± 7.7/368.9 ± 8.2) versus controls (tibial/peroneal: 266.0 ± 11.0/276.8 ± 9.7, p   〈  0.0001). In contrast, T2 relaxation time was significantly higher in controls (tibial/peroneal: 82.0 ± 2.1/78.3 ± 1.7) versus MS (tibial/peroneal: 64.3 ± 1.0/61.2 ± 0.9, p   〈  0.0001). Proximal tibial and peroneal nerve caliber was higher in MS (tibial: 52.4 ± 2.1mm 2 , peroneal: 25.4 ± 1.3mm 2 ) versus controls (tibial: 45.2 ± 1.4mm 2 , p   〈  0.0015; peroneal: 21.3 ± 0.7mm 2 , p  = 0.0049). Interpretation Peripheral nerve lesions could be visualized and quantified in MS in vivo by high‐resolution MRN. Lesions are defined by an increase of proton spin density and a decrease of T2 relaxation time, indicating changes in the microstructural organization of the extracellular matrix in peripheral nerve tissue in MS. By showing involvement of the peripheral nervous system in MS, this proof‐of‐concept study may offer new insights into the pathophysiology and treatment of MS. Ann Neurol 2017;82:676–685
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2037912-2
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  • 6
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 91, No. 7 ( 2018-08-14), p. e625-e634
    Abstract: To detect, localize, and quantify peripheral nerve lesions in amyloid light chain (AL) amyloidosis by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings. Methods We prospectively examined 20 patients with AL-polyneuropathy (PNP) and 25 age- and sex-matched healthy volunteers. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into mild and moderate PNP. MRN in a 3.0 tesla scanner with anatomical coverage from the lumbosacral plexus and proximal thigh down to the tibiotalar joint was performed by using T2-weighted and dual-echo 2-dimensional sequences with spectral fat saturation and a 3-dimensional, T2-weighted inversion recovery sequence. Besides evaluation of nerve T2-weighted signal, detailed quantification of nerve injury by morphometric (nerve caliber) and microstructural MRN markers (proton spin density, T2 relaxation time) was conducted. Results Nerve T2-weighted signal increase correlated with disease severity: moderate (420.2 ± 60.1) vs mild AL-PNP (307.2 ± 17.9; p = 0.0003) vs controls (207.0 ± 6.4; p 〈 0.0001). Proton spin density was also higher in moderate (tibial: 525.5 ± 53.0; peroneal: 553.6 ± 64.5; sural: 492.0 ± 56.6) and mild AL-PNP (tibial: 431.6 ± 22.0; peroneal: 457.6 ± 21.7; sural: 404.8 ± 25.2) vs controls (tibial: 310.5 ± 14.1; peroneal: 313.6 ± 11.6; sural: 261.7 ± 11.0; p 〈 0.0001 for all nerves). T2 relaxation time was elevated in moderate AL-PNP only (tibial: p = 0.0106; peroneal: p = 0.0070; sural: p = 0.0190). Tibial nerve caliber was higher in moderate (58.0 ± 8.8 mm 3 ) vs mild AL-PNP (46.5 ± 2.5 mm 3 ; p = 0.008) vs controls (39.1 ± 1.2 mm 3 ; p 〈 0.0001). Conclusions MRN detects and quantifies peripheral nerve injury in AL-PNP in vivo with high sensitivity and in close correlation with the clinical stage. Quantitative parameters are feasible new imaging biomarkers for the detection of early AL-PNP and might help to monitor microstructural nerve tissue changes under treatment.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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  • 7
    Online Resource
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    Springer Science and Business Media LLC ; 2015
    In:  Orphanet Journal of Rare Diseases Vol. 10, No. Suppl 1 ( 2015), p. P40-
    In: Orphanet Journal of Rare Diseases, Springer Science and Business Media LLC, Vol. 10, No. Suppl 1 ( 2015), p. P40-
    Type of Medium: Online Resource
    ISSN: 1750-1172
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 2225857-7
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  • 8
    In: Annals of Clinical and Translational Neurology, Wiley, Vol. 7, No. 5 ( 2020-05), p. 799-807
    Abstract: To quantify peripheral nerve lesions in symptomatic and asymptomatic hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PNP) by analyzing the magnetization transfer ratio (MTR) of the sciatic nerve, and to test its potential as a novel biomarker for macromolecular changes. Methods Twenty‐five patients with symptomatic ATTRv‐PNP, 30 asymptomatic carriers of the mutant transthyretin gene (mut TTR ), and 20 age‐/sex‐matched healthy controls prospectively underwent magnetization transfer contrast imaging at 3 Tesla. Two axial three‐dimensional gradient echo sequences with and without an off‐resonance saturation rapid frequency pulse were conducted at the right distal thigh. Sciatic nerve regions of interest were manually drawn on 10 consecutive axial slices in the images without off‐resonance saturation, and then transferred to the corresponding slices that were generated by the sequence with the off‐resonance saturation pulse. Subsequently, the MTR and cross‐sectional area (CSA) of the sciatic nerve were evaluated. Detailed neurologic and electrophysiologic examinations were conducted in all ATTRv‐PNP patients and mut TTR ‐carriers. Results Sciatic nerve MTR and CSA reliably differentiated between ATTRv‐PNP, mut TTR ‐carriers, and controls. MTR was lower in ATTRv‐PNP (26.4 ± 0.7; P   〈  0.0001) and in mut TTR ‐carriers (32.6 ± 0.8; P  = 0.0005) versus controls (39.4 ± 2.1), and was also lower in ATTRv‐PNP versus mut TTR ‐carriers ( P  = 0.0009). MTR correlated negatively with the NIS‐LL and positively with CMAPs and SNAPs. CSA was higher in ATTRv‐PNP (34.3 ± 1.7 mm 3 ) versus mut TTR ‐carriers (26.0 ± 1.1 mm 3 ; P  = 0.0005) and versus controls (20.4 ± 1.2 mm 3 ; P   〈  0.0001). CSA was also higher in mut TTR ‐carriers versus controls. Interpretation MTR is a novel imaging marker that can quantify macromolecular changes in ATTRv‐PNP and differentiate between symptomatic ATTRv‐PNP and asymptomatic mut TTR ‐carriers and correlates with electrophysiology.
    Type of Medium: Online Resource
    ISSN: 2328-9503 , 2328-9503
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2740696-9
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  • 9
    In: European Journal of Neurology, Wiley, Vol. 29, No. 2 ( 2022-02), p. 573-582
    Abstract: We characterized and quantified peripheral nerve damage in alcohol‐dependent patients (ADP) by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings. Methods Thirty‐one adult patients with a history of excessive alcohol consumption and age‐/sex‐matched healthy controls were prospectively examined. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into ADP with alcohol‐related polyneuropathy (ALN) and without ALN (Non‐ALN). 3T MRN with anatomical coverage from the proximal thigh down to the tibiotalar joint was performed using dual‐echo 2‐dimensional relaxometry sequences with spectral fat saturation. Detailed quantification of nerve injury by morphometric (cross‐sectional area [CSA]) and microstructural MRN markers (proton spin density [ρ] , apparent T2‐relaxation‐time [T2 app ]) was conducted in all study participants. Results MRN detected nerve damage in ADP with and without ALN. A proximal‐to‐distal gradient was identified for nerve T2‐weighted (T2w)‐signal and T2 app in ADP, indicating a proximal predominance of nerve lesions. While all MRN markers differentiated significantly between ADP and controls, microstructural markers were able to additionally differentiate between subgroups: tibial nerve ρ at thigh level was increased in ALN ( p  〈  0.0001) and in Non‐ALN ( p  = 0.0052) versus controls, and T2 app was higher in ALN versus controls ( p  〈  0.0001) and also in ALN versus Non‐ALN ( p  = 0.0214). T2w‐signal and CSA were only higher in ALN versus controls. Conclusions MRN detects and quantifies peripheral nerve damage in ADP in vivo even in the absence of clinically overt ALN. Microstructural markers (T2 app , ρ) are most suitable for differentiating between ADP with and without manifest ALN, and may help to elucidate the underlying pathomechanism in ALN.
    Type of Medium: Online Resource
    ISSN: 1351-5101 , 1468-1331
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2020241-6
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  • 10
    In: Investigative Radiology, Ovid Technologies (Wolters Kluwer Health), Vol. 57, No. 5 ( 2022-5), p. 301-307
    Abstract: Multi spin echo (MSE) sequences are often used for obtaining T2-relaxometry data as they provide defined echo times (TEs). Due to their time-consuming acquisition, they are frequently replaced by turbo spin echo (TSE) sequences that in turn bear the risk of systematic errors when analyzing small structures or lesions. With this study, we aim to test whether T2-relaxometry data derived from either dual-echo TSE or 12-echo MSE sequences are equivalent for quantifying peripheral nerve lesions. Hereditary transthyretin (ATTRv) amyloidosis was chosen as a surrogate disease, as it allows the inclusion of both asymptomatic carriers of the underlying variant transthyretin gene (var TTR ) and symptomatic ATTRv amyloidosis patients. Materials and Methods Overall, 50 participants with genetically confirmed var TTR (20 clinically symptomatic ATTRv amyloidosis; 4 females, 16 males; mean age, 61.8 years; range, 33–76 years; and 30 asymptomatic var TTR -carriers; 18 females, 12 males; mean age, 43.1 years; range, 21–62 years), and 30 healthy volunteers (13 females, 17 males, mean age 41.3 years, range 22–73) were prospectively included and underwent magnetic resonance neurography at 3 T. T2-relaxometry was performed by acquiring an axial 2-dimensional dual-echo TSE sequence with spectral fat saturation (TE 1 /TE 2 , 12/73 milliseconds; TR, 5210 milliseconds; acquisition time, 7 minutes, 30 seconds), and an axial 2-dimensional MSE sequence with spectral fat saturation and with 12 different TE (TE 1 , 10 milliseconds to TE 12 , 120 milliseconds; ΔTE, 10 milliseconds; TR, 3000 milliseconds; acquisition time, 11 minutes, 23 seconds) at the right mid to lower thigh. Sciatic nerve regions of interest were manually drawn in ImageJ on 10 central slices per participant and sequence, and the apparent T2-relaxation time (T2app) and proton spin density (ρ) were calculated individually from TSE and MSE relaxometry data. Results Linear regression showed that T2app values obtained from the dual-echo TSE (T2app TSE ), and those calculated from the 12-echo MSE (T2app MSE ) were mathematically connected by a factor of 1.3 throughout all groups (controls: 1.26 ± 0.02; var TTR- carriers: 1.25 ± 0.02; symptomatic ATTRv amyloidosis: 1.28 ± 0.02), whereas a factor of 0.5 was identified between respective ρ values (controls: 0.47 ± 0.01; var TTR- carriers: 0.47 ± 0.01; symptomatic ATTRv amyloidosis: 0.50 ± 0.02). T2app calculated from both TSE and MSE, distinguished between symptomatic ATTRv (T2app TSE 66.38 ± 2.6; T2 appMSE 84.6 ± 3.3) and controls (T2app TSE 58.1 ± 1.0, P = 0.0028; T2app MSE 72.8 ± 0.7, P 〈 0.0001), whereas differences between var TTR- carriers (T2app TSE 61.8 ± 1.5; T2app MSE 76.7 ± 1.3) and ATTRv amyloidosis were observed only for T2app MSE ( P = 0.0082). The ρ value differentiated well between healthy controls (ρ TSE 365.1 ± 7.2; ρ MSE 170.4 ± 3.8) versus var TTR- carriers (ρ TSE 415.7 ± 9.8, P = 0.0027; ρ MSE 193.7 ± 5.3, P = 0.0398) and versus symptomatic ATTRv amyloidosis (ρ TSE 487.8 ± 17.9; ρ MSE 244.7 ± 13.1, P 〈 0.0001, respectively), but also between var TTR -carriers and ATTRv amyloidosis (ρ TSE P = 0.0001; ρ MSE P 〈 0.0001). Conclusions Dual-echo TSE and 12-echo MSE sequences provide equally robust and reliable T2-relaxometry data when calculating T2app and ρ. Due to their shorter acquisition time and higher resolution, TSE sequences may be preferred in future magnetic resonance imaging protocols. As a secondary result, ρ can be confirmed as a sensitive biomarker to detect early nerve lesions as it differentiated best among healthy controls, asymptomatic var TTR -carriers, and symptomatic ATTRv amyloidosis, whereas T2app might be beneficial in already manifest ATTRv amyloidosis.
    Type of Medium: Online Resource
    ISSN: 1536-0210 , 0020-9996
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2041543-6
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