Echogenicity of Brain Structures in Huntington’s Disease Patients Evaluated by Transcranial Sonography – Magnetic Resonance Fusion Imaging using Virtual Navigator and Digital Image Analysis

Abstract

Purpose Transcranial sonography (TCS) magnetic resonance (MR) fusion imaging and digital image analysis are useful tools for the evaluation of various brain pathologies. This study aimed to compare the echogenicity of predefined brain structures in Huntington’s disease (HD) patients and healthy controls by TCS-MR fusion imaging using Virtual Navigator and digitized image analysis.

Materials and Methods The echogenicity of the caudate nucleus (CN), substantia nigra (SN), lentiform nucleus (LN), insula, and brainstem raphe (BR) evaluated by TCS-MR fusion imaging using digitized image analysis was compared between 21 HD patients and 23 healthy controls. The cutoff values of echogenicity indices for the CN, LN, insula, and BR with optimal sensitivity and specificity were calculated using receiver operating characteristic analysis.

Results The mean echogenicity indices for the CN (67.0±22.6 vs. 37.9±7.6, p<0.0001), LN (110.7±23.6 vs. 59.7±11.1, p<0.0001), and insula (121.7±39.1 vs. 70.8±23.0, p<0.0001) were significantly higher in HD patients than in healthy controls. In contrast, BR echogenicity (24.8±5.3 vs. 30.1±5.3, p<0.001) was lower in HD patients than in healthy controls. The area under the curve was 90.9%, 95.5%, 84.1%, and 81.8% for the CN, LN, insula, and BR, respectively. The sensitivity and specificity were 86% and 96%, respectively, for the CN and 90% and 100%, respectively, for the LN.

Conclusion Increased CN, LN, and insula echogenicity and decreased BR echogenicity are typical findings in HD patients. The high sensitivity and specificity of the CN and LN hyperechogenicity in TCS-MR fusion imaging make them promising diagnostic markers for HD.

Zusammenfassung

Ziel Transkranielle Sonografie (TCS), Magnetresonanz-Fusionsbildgebung (MR-Fusionsbildgebung) und digitale Bildanalyse sind nützliche Werkzeuge für die Beurteilung verschiedener Hirnpathologien. Ziel dieser Studie war es, durch TCS-MR-Fusionsbildgebung mittels Virtual Navigator und digitaler Bildanalyse die Echogenität vordefinierter Hirnstrukturen bei Patienten mit der Huntington-Krankheit (HD) und gesunden Kontrollpersonen zu vergleichen.

Material und Methoden Die Echogenität des Nucleus caudatus (NC), der Substantia nigra (SN), des Nucleus lentiformis (NL), der Insula und der Hirnstamm-Raphe (BR), die mittels TCS-MR-Fusionsbildgebung und digitalisierter Bildanalyse bewertet wurde, wurde bei 21 Patienten mit Huntington-Krankheit und 23 gesunden Kontrollpersonen verglichen. Die Cutoff-Werte der Echogenitätsindizes für NC, NL, Insula und BR mit optimaler Sensitivität und Spezifität wurden mittels ROC-Analyse (Receiver Operating Characteristic Analyse) berechnet.

Ergebnisse Bei HD-Patienten im Vergleich zu gesunden Kontrollen waren die mittleren Echogenitätsindizes signifikant höher für den NC (67,0 ± 22,6 vs. 37,9 ± 7,6; p<0,0001), den NL (110,7 ± 23,6 vs. 59,7 ± 11,1; p<0,0001) und die Insula (121,7 ± 39,1 vs. 70,8 ± 23,0; p<0,0001). Im Gegensatz dazu war die BR-Echogenität bei HD-Patienten geringer als bei gesunden Kontrollpersonen (24,8 ± 5,3 vs. 30,1 ± 5,3; p<0,001). Die AUC betrug 90,9% für den NC, 95,5% für den NL, 84,1% für die Insula und 81,8% für die BR. Die Sensitivität und Spezifität betrugen 86% bzw. 96% für den NC und 90% bzw. 100% für den NL.

Schlussfolgerung Erhöhte Echogenität von NC, NL und Insula und verringerte BR-Echogenität sind typische Befunde bei HD-Patienten. Die hohe Sensitivität und Spezifität der Hyperechogenität von NC und NL in der TCS-MR-Fusionsbildgebung machen diese zu vielversprechenden diagnostischen Markern für HD.

Keywords

Head/Neck - Neurology - Physics and Technology

Publication History

Received: 07 November 2022

Accepted after revision: 29 March 2023

Article published online:
24 May 2023

• References

• 1 Macdonald M. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 1993; 72 (06) 971-983
• 2 Walker FO. Huntington’s disease. The Lancet 2007; 369: 218-228
• 3 Berg D, Godau J, Walter U. Transcranial sonography in movement disorders. Lancet Neurol 2008; 7 (11) 1044-1055
• 4 Kostić V, Mijajlović M, Smajlović D. et al. Transcranial brain sonography findings in two main variants of progressive supranuclear palsy. Eur J Neurol 2013; 20 (03) 552-557
• 5 Mašková J, Školoudík D, Burgetová A. et al. Comparison of transcranial sonography-magnetic resonance fusion imaging in Wilson's and early-onset Parkinson's diseases. Parkinsonism Relat Disord 2016; 28: 87-93
• 6 Walter U, Skowrońska M, Litwin T. et al. Lenticular nucleus hyperechogenicity in Wilson’s disease reflects local copper, but not iron accumulation. J Neural Transm 2014; 121 (10) 1273-1279
• 7 Walter U, Školoudík D. Transcranial sonography (TCS) of brain parenchyma in movement disorders: quality standards, diagnostic applications and novel technologies. Ultraschall in Med 2014; 35 (04) 322-331
• 8 Yilmaz R, Pilotto A, Roeben B. et al. Structural ultrasound of the medial temporal lobe in Alzheimer’s disease. Ultraschall in Med 2017; 38 (03) 294-300
• 9 Zhou HY, Huang P, Sun Q. et al. The role of substantia nigra sonography in the differentiation of Parkinson’s disease and multiple system atrophy. Transl Neurodegener 2018; 7 (01) 1-7
• 10 Postert T, Lack B, Kuhn W. et al. Basal ganglia alterations and brain atrophy in Huntington’s disease depicted by transcranial real time sonography. J Neurol Neurosurg Psychiatry 1999; 67 (04) 457-462
• 11 Skoloudík D, Walter U. Method and validity of transcranial sonography in movement disorders. Int Rev Neurobiol 2010; 90: 7-34
• 12 Krogias C, Strassburger K, Eyding J. et al. Depression in patients with Huntington disease correlates with alterations of the brain stem raphe depicted by transcranial sonography. J Psychiatry Neurosci 2011; 36 (03) 187-194
• 13 Lambeck J, Niesen WD, Reinhard M. et al. Substantia nigra hyperechogenicity in hypokinetic Huntington's disease patients. J Neurol 2015; 262 (03) 711-717
• 14 Saft C, Hoffmann R, Strassburger-Krogias K. et al. Echogenicity of basal ganglia structures in different Huntington's disease phenotypes. J Neural Transm 2015; 122 (06) 825-833
• 15 Witkowski G, Jachinska K, Stepniak I. et al. Alterations in transcranial sonography among Huntington's disease patients with psychiatric symptoms. J Neural Transm 2020; 127 (07) 1047-1055
• 16 Školoudík D, Bártová P, Mašková J. et al. Transcranial Sonography of the Insula: Digitized Image Analysis of Fusion Images with Magnetic Resonance. Ultraschall in Med 2016; 37 (06) 604-608
• 17 Školoudík D, Mašková J, Dušek P. et al. Digitized Image Analysis of Insula Echogenicity Detected by TCS-MR Fusion Imaging in Wilson's and Early-Onset Parkinson's Diseases. Ultrasound Med Biol 2020; 46 (03) 842-848
• 18 Bachoud-Lévi AC, Ferreira J, Massart R. et al. International Guidelines for the Treatment of Huntington’s Disease. Front Neurol 2019; 10: 710
• 19 Blahuta J, Soukup T, Jelinkova M. et al. A new program for highly reproducible automatic evaluation of the substantia nigra from transcranial sonographic images. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 158 (04) 621-627
• 20 Šilhán P, Jelínková M, Walter U. et al. Transcranial sonography of brainstem structures in panic disorder. Psychiatry Res 2015; 234 (01) 137-143
• 21 Skoloudík D, Jelínková M, Blahuta J. et al. Transcranial sonography of the substantia nigra: digital image analysis. AJNR Am J Neuroradiol 2014; 35 (12) 2273-2278
• 22 Liu X. Classification accuracy and cut point selection. Stat Med 2012; 31 (23) 2676-2686
• 23 Fukunaga M, Li TQ, van Gelderen P. et al. Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast. Proc Natl Acad Sci U S A 2010; 107 (08) 3834-3839
• 24 Chen L, Hua J, Ross CA. et al. Altered brain iron content and deposition rate in Huntington’s disease as indicated by quantitative susceptibility MRI. J Neurosci Res 2019; 97 (04) 467-479
• 25 Martínez-Horta S, Perez-Perez J, Sampedro F. et al. Structural and metabolic brain correlates of apathy in Huntington's disease. Mov Disord 2018; 33 (07) 1151-1159
• 26 Peinemann A, Schuller S, Pohl C. et al. Executive dysfunction in early stages of Huntington’s disease is associated with striatal and insular atrophy: a neuropsychological and voxel-based morphometric study. J Neurol Sci 2005; 239 (01) 11-19
• 27 Tai YF, Pavese N, Gerhard A. et al. Microglial activation in presymptomatic Huntington’s disease gene carriers. Brain 2007; 130: 1759-1766
• 28 Du X, Pang TY, Hannan AJ. A Tale of Two Maladies? Pathogenesis of Depression with and without the Huntington’s Disease Gene Mutation. Front Neurol 2013; 4: 81
• 29 Paulsen JS, Wang C, Duff K. et al. Challenges assessing clinical endpoints in early Huntington disease. Mov Disord 2010; 25 (15) 2595-2603