Transcranial Sonography Findings in Alzheimer’s Disease: A New Imaging Biomarker

Abstract

Objective To validate transcranial sonography (TCS) as a novel imaging tool for the assessment of medial temporal lobe (MTL) atrophy (MTA).

Materials and Methods Participants with Alzheimer’s disease (AD, n = 30) and age-sex-matched controls (n = 30) underwent TCS and MRI. On TCS, MTL structures (choroidal fissure (CF) and temporal horn (TH)) were measured and combined to create an MTA score in sonography (MTA-S). Furthermore, both THs and the third ventricle were combined to form the ventricle enlargement score in sonography (VES-S). On MRI, the MTL was evaluated by linear measurements, MTA scale and hippocampal volumetry. Validation was performed by comparing imaging methods and the patient group.

Results Intraclass correlations for CF and TH showed substantial intra/inter-rater reliability (> 0.80). TCS and MRI showed strong to moderate correlation regarding TH (right = 0.88, left = 0.89) and CF (right = 0.70, left = 0.47). MTA-S correlated significantly with the hippocampal volume (right = –0.51, left = –0.47), predicted group membership in logistic regression (Exp(B) right = 3.0, left = 2.7), and could separate AD patients from controls (AUC = 0.93). An MTA-S of 6 mm and 10 mm discriminated MRI MTA scores 0–1 (from 2–4) and MTA score 4 (from 0–3) with 100 % specificity, respectively. VES-S also showed a moderate correlation with the hippocampal volume (r = –0.66) and could differentiate AD patients from controls (AUC = 0.93).

Conclusion Our results suggest that TCS may be an alternative imaging tool for the assessment of MTL atrophy and ventricular enlargement for patients in whom MRI scanning is not possible. Additionally, TCS offers a practical, patient-friendly and inexpensive option for the screening and follow-up of individuals with AD.

Zusammenfassung

Ziel Validierung der transkraniellen Sonografie (TCS) als neue Bildgebung zur Beurteilung der MTA, der Atrophie des medialen Temporallappens (MTL).

Material und Methoden Bei allen Teilnehmern, Patienten mit Morbus Alzheimer (n = 30) sowie alters- und geschlechtsspezifischen Kontrollen (n = 30), wurde eine TCS und MRT durchgeführt. Bei der TCS wurden die MTL-Strukturen (Choroidalfissur (CF) und Temporalhorn (TH)) gemessen und zu einem sonografischen MTA-Score (MTA-S) kombiniert. Darüber hinaus wurden die beiden THs und der dritte Ventrikel kombiniert, um einen sonografischen Score für die Ventrikelerweiterung (VES-S) zu erstellen. In der MRT wurden der MTL durch lineare Messungen, die MTA-Skala und die Hippocampus-Volumetrie bewertet. Die Validierung erfolgte durch den Vergleich der bildgebenden Verfahren und der Patientengruppe.

Ergebnis Die Intraklassenkorrelationen für CF und TH zeigten eine beträchtliche Intra-/Interrater-Reliabilität (> 0,80). TCS und MRI zeigten eine starke bis moderate Übereinstimmung in Bezug auf die TH (rechts = 0,88; links = 0,89) und die CF (rechts = 0,70; links = 0,47). Der MTA-S zeigte eine signifikante Korrelation mit dem Hippocampus-Volumen (rechts = –0,51; links = –0,47), prognostizierte die Zugehörigkeit zu der Gruppe in der logistischen Regression (Exp(B) rechts = 3,0; links = 2,7) und konnte zwischen Patienten und Kontrollen trennen (AUC = 0,93). Ein MTA-S von 6 mm bzw. 10 mm konnte jeweils einen MRT-MTA-Score 0–1 (von 2–4) von einen MTA-Score 4 (von 0–3) mit 100 % Spezifität unterscheiden. Der VES-S zeigte auch eine moderate Übereinstimmung mit dem Hippocampus-Volumen (r = –0,66) und konnte zwischen Alzheimer-Patienten und Kontrollen differenzieren (AUC = 0,93).

Schlussfolgerung Unsere Ergebnisse deuten darauf hin, dass die TCS ein alternatives bildgebendes Verfahren zur Beurteilung des MTL und der Ventrikelerweiterung bei Patienten sein könnte, bei denen eine MRT-Untersuchung nicht durchführbar ist. Darüber hinaus ist die TCS für das Screening und die Nachsorge von Alzheimer-Patienten eine praktische, patientenfreundliche und kostengünstige Option.

Key words

Alzheimer’s disease - dementia - medial temporal lobe - transcranial sonography

^* These authors share senior authorship.

Publication History

Received: 29 October 2019

Accepted: 28 February 2020

Article published online:
03 June 2020

• References

• 1 Frisoni GB, Bocchetta M, Chetelat G. et al. Imaging markers for Alzheimer disease: Which vs how. Neurology 2013; 81: 487-500
• 2 Jack CR, Barkhof F, Bernstein MA. et al. Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criterion for Alzheimer’s disease. In: Alzheimer’s and Dementia. 2011
• 3 Häussermann P, Bartsch T, Granert O. Brain functional imaging in preclinical Alzheimer’s disease. In: Neuromethods. 2018
• 4 Jack CR, Petersen RC, Xu Y. et al. Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology 2000; 55: 484-489
• 5 Matsuda H. Voxel-based Morphometry of Brain MRI in Normal Aging and Alzheimer’s Disease. Aging Dis 2013; 4: 29-37
• 6 Flores RDE, Joie RLA, Che L. Structural Imaging of Hippocampal Subfields in Healthy Aging and Alzheimer’S Disease. Neuroscience 2015; 309: 29-50
• 7 Scheltens P, Leys D, Barkhof F. et al. Atrophy of medial temporal lobes on MRI in ‘probable’ Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry BMJ Publishing Group 1992; 55: 967-972
• 8 Kipps CM, Davies RR, Mitchell J. et al. Clinical significance of lobar atrophy in frontotemporal dementia: Application of an MRI visual rating scale. Dement Geriatr Cogn Disord 2007; 23: 334-342
• 9 Koedam ELGE, Lehmann M, van der Flier WM. et al. Visual assessment of posterior atrophy development of a MRI rating scale. Eur Radiol 2011; 21: 2618-2625
• 10 Harper L, Fumagalli GG, Barkhof F. et al. MRI visual rating scales in the diagnosis of dementia: Evaluation in 184 post-mortem confirmed cases. Brain Oxford University Press 2016; 139: 1211-1225
• 11 Duara R, Loewenstein DA, Shen Q. et al. The utility of age-specific cut-offs for visual rating of medial temporal atrophy in classifying Alzheimer’s disease, MCI and cognitively normal elderly subjects. Front Aging Neurosci 2013; 5: 47
• 12 Frisoni GB, Fox NC, Jack CR. et al. The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol 2010; 6: 67-77
• 13 McKhann GM, Knopman DS, Chertkow H. et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 263-269
• 14 Yilmaz R, Pilotto A, Roeben B. et al. Structural Ultrasound of the Medial Temporal Lobe in Alzheimer’s Disease | Struktureller Ultraschall des medialen Temporallappens bei Alzheimer-Demenz. Ultraschall der Medizin 2016; DOI: 10.1055/s-0042-107150.
• 15 Walter U, Školoudík D. Transcranial Sonography (TCS) of Brain Parenchyma in Movement Disorders: Quality Standards, Diagnostic Applications and Novel Technologies. Ultraschall der Medizin – Eur J Ultrasound 2014; 35: 322-331
• 16 Yilmaz R, Berg D. Evaluating a Patient with Transcranial Sonography to Look for Echogenicity. Mov Disord Clin Pract Wiley-Blackwell 2017; 4: 907
• 17 Fischl B, Salat DH, Busa E. et al. Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain. Neuron Cell Press 2002; 33: 341-355
• 18 Hanert A, Pedersen A, Bartsch T. Transient hippocampal CA1 lesions in humans impair pattern separation performance. Hippocampus 2019; DOI: 10.1002/hipo.23073.
• 19 Finke C, Prüss H, Heine J. et al. Evaluation of Cognitive Deficits and Structural Hippocampal Damage in Encephalitis With Leucine-Rich, Glioma-Inactivated 1 Antibodies. JAMA Neurol 2017; 74: 50-59
• 20 Wollenweber FA, Schomburg R, Probst M. et al. Width of the third ventricle assessed by transcranial sonography can monitor brain atrophy in a time- and cost-effective manner – Results from a longitudinal study on 500 subjects. Psychiatry Res – Neuroimaging Elsevier Ireland Ltd 2011; 191: 212-216
• 21 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet (London, England) 1986; 1: 307-310
• 22 Rix A, Lederle W, Theek B. et al Advanced Ultrasound Technologies for Diagnosis and Therapy. J Nucl Med 2018: jnumed.117.200030
• 23 Ng A, Swanevelder J. Resolution in ultrasound imaging. Contin Educ Anaesthesia, Crit Care Pain 2011; DOI: 10.1093/bjaceaccp/mkr030.
• 24 Jack CR, Petersen RC, Xu Y. et al. Rate of medial temporal lobe atrophy in typical aging and Alzheimer’s disease. Neurology 1998; DOI: 10.1212/wnl.51.4.993.
• 25 Bresciani L, Rossi R, Testa C. et al. 32. LTM visual vs volumetria. 2005; 17: 8-13
• 26 Favaretto S, Walter U, Baracchini C. et al. Accuracy of transcranial brain parenchyma sonography in the diagnosis of dementia with Lewy bodies. Eur J Neurol 2016; 23: 1322-1328
• 27 Liman J, Wellmer A, Rostasy K. et al. Transcranial ultrasound in neurodegeneration with brain iron accumulation (NBIA). Eur J Paediatr Neurol 2012; 16: 175-178
• 28 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
• 29 Scheltens P, Fox N, Barkhof F. et al. Structural magnetic resonance imaging in the practical assessment of dementia: beyond exclusion. Lancet Neurol 2002; 1: 13-21
• 30 Bradshaw PJ, Stobie P, Knuiman MW. et al. Trends in the incidence and prevalence of cardiac pacemaker insertions in an ageing population. Open Hear 2014; 1: 1-6
• 31 Frisoni GB, Geroldi C, Beltramello A. et al. Radial width of the temporal horn: a sensitive measure in Alzheimer disease. AJNR Am J Neuroradiol 2002; 23: 35-47
• 32 Foster GR, Scott DA, Payne S. The use of CT scanning in dementia. A systematic review. Int J Technol Assess Health Care 1999; DOI: 10.1017/S0266462399152115.
• 33 Henneman WJP, Sluimer JD, Barnes J. et al. Hippocampal atrophy rates in Alzheimer disease: Added value over whole brain volume measures. Neurology 2009; DOI: 10.1212/01.wnl.0000344568.09360.31.
• 34 Frankó E, Joly O. Alzheimer’s Disease Neuroimaging Initiative. Evaluating Alzheimer’s disease progression using rate of regional hippocampal atrophy. PLoS One 2013; 8: e71354
• 35 Fox NC, Warrington EK, Freeborough PA. et al. Presymptomatic hippocampal atrophy in Alzheimer’s disease. A longitudinal MRI study. Brain 1996; 119: 2001-2007
• 36 Yilmaz R, Berg D. Transcranial B-Mode Sonography in Movement Disorders. In: International Review of Neurobiology. 143. 2018: 179-212
• 37 Prestel J, Schweitzer KJ, Hofer A. et al. Predictive value of transcranial sonography in the diagnosis of Parkinson’s disease. Mov Disord 2006; 21: 1763-1765
• 38 Vernooij MW, Pizzini FB, Schmidt R. et al. Dementia imaging in clinical practice: a European-wide survey of 193 centres and conclusions by the ESNR working group. Neuroradiology 2019; 633-642