T2 Hyperintensity of Medial Lemniscus: Higher Threshold Application to ROI Measurements is More Accurate in Predicting Small Vessel Disease
Michael M. Hakky MD
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorKaan D. Erbay BS
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorEdward Brewer MD
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorJennifer B. Midle MD
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorRobert French MD
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorSami H. Erbay MD
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorMichael M. Hakky MD
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorKaan D. Erbay BS
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorEdward Brewer MD
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorJennifer B. Midle MD
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorRobert French MD
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorSami H. Erbay MD
From the Department of Radiology, Lahey Clinic Medical Center, 41 Mall Rd, Burlington, MA 01805; Department of Radiology, Tufts Medical Center, 750 Washington St. Boston, MA 02111; and Tufts University, Center for Biostatistics, 75 Kneeland Street, Boston, MA 02111.
Search for more papers by this authorGrant Support: This study is partially funded by Wise Educational Grant, # 20073519, Lahey Clinic, Burlington, MA.
J Neuroimaging 2013;23:345-351.
Abstract
ABSTRACT
BACKGROUND
Medial lemniscus T2 hyperintensity (MLH) has been recently demonstrated as potential imaging marker for small vessel disease (SVD). Our purpose in this study is to improve accuracy of regions of interest (ROI) analysis for this imaging finding.
METHODS AND METHODS
Two neuroradiologists retrospectively reviewed 103 consecutive outpatient brain MRI. Medial lemniscus signal in dorsal pons was evaluated; visually on FLAIR and with ROI on T2. Original MRI interpretations were divided into three categories; SVD, multiple sclerosis (MS), and nonspecific WM changes (non).
RESULTS
Thirty-seven patients had SVD, 14 patients had MS, 52 had Non. Visual MLH was seen exclusively with SVD and was generally bilateral. Patients with visual MLH belonged to advanced SVD by imaging and clinical parameters. Compared to visual data, ROI analyses of MLH has been known to be compounded by false positives and negatives at low threshold (20% of adjacent to normal brainstem signal). With application of higher ROI threshold (25%), false positives were eliminated but false negatives increased. ROI analyses of MLH by experienced neuroradiologist were more reliable.
CONCLUSION
MLH seen on high threshold ROI analysis is a reliable radiologic marker in predicting SVD. ROI analysis of MLH should be performed by an experienced neuroradiologist.
References
- 1
Barkhof F,
Scheltens P.
Imaging of white matter lesions.
Cerebrovascular Diseases
. 2002; 13(Suppl 2): 21–30.
10.1159/000049146 Google Scholar
- 2 Whitman GT, Tang Y, Lin A, Baloh RW. A prospective study of cerebral white matter abnormalities in older people with gait dysfunction. [Erratum appears in Neurology 2001 Nov 27;57(10):1942. Note: Tang T [corrected to Tang Y]] Neurology 57(6): 990–994, 2001.
- 3 Fukui T, Sugita K, Kawamura M, et al. Differences in factors associated with silent and symptomatic MRI T2 hyperintensity lesions. J Neurol 1997; 244(5): 293–298.
- 4 Staekenborg SS, van Straaten EC, van der Flier WM, et al. Small vessel versus large vessel vascular dementia: risk factors and MRI findings. J Neurol 2008; 255(11): 1644–1651.
- 5 Norrving B. Lacunar infarcts: no black holes in the brain are benign. Prac. Neurol. 2008; 8(4): 222–228.
- 6 Erbay SH, Brewer E, French R, et al. T2 hyperintensity of medial lemniscus is an indicator of small-vessel disease. Am J Roentgenol 2012; 199(1): 163–168.
- 7 Carpenter MB, Sutin J. Human Neuroanatomy , Chapters 10-12, 8th Edition, Williams and Wilkins, Baltimore, MD, USA . 1983.
- 8 Rasmussen AT, Peyton WT. The course and termination of the medial lemniscus in man. J Comp Neurol 1948; 88(3): 411–424.
- 9 Altman DG. Some common problems in medical research. In: Practical statistics for medical research. New York , NY : Chapman & Hall, 1991: 403–409.
- 10 Landis RJ, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33: 159–174.
- 11 Renard D, Castelnovo G, Bousquet PJ, et al. Brain MRI findings in long-standing and disabling multiple sclerosis in 84 patients. Clin Neurol Neurosurg 2010; 112(4): 286–290.
- 12 Bae S, Kim JE, Hwang J, et al. Increased prevalence of white matter hyperintensities in patients with panic disorder. J Psychopharmacol 2010; 24(5): 717–723.
- 13 Brockmann K, Dreha-Kulaczewski S, Dechent P, et al. Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations. J Neurol 2008; 255(7): 1049–1058.
- 14 Kimura A, Sakurai T, Tanaka Y, et al. Proteomic analysis of autoantibodies in neuropsychiatric systemic lupus erythematosus patient with white matter hyperintensities on brain MRI. Lupus 2008; 17(1): 16–20.
- 15 Bleecker ML, Ford DP, Vaughan CG, et al. The association of lead exposure and motor performance mediated by cerebral white matter change. Neurotoxicology 2007; 28(2): 318–323.
- 16 Gladstone JP, Dodick DW. Migraine and cerebral white matter lesions: when to suspect cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Neurologist 2005; 11(1): 19–29.
- 17 Wardlaw JM, Ferguson KJ, Graham C. White matter hyperintensities and rating scales-observer reliability varies with lesion load. J Neurol 2004; 251(5): 584–590.
- 18 Smith EE, Nandigam KR, Chen YW, et al. MRI markers of small vessel disease in lobar and deep hemispheric intracerebral hemorrhage. Stroke 2010; 41(9): 1933–1938.
- 19 Schiffmann R, van der Knaap MS. Invited article: an MRI-based approach to the diagnosis of white matter disorders. Neurology 2009; 72(8): 750–759.
- 20 Finsterer J. [MELAS syndrome as a differential diagnosis of ischemic stroke]. [Review][83 refs][German] MELAS-Syndrom als Differenzialdiagnose des juvenilen ischamischen Insultes. Fortschritte der Neurologie-Psychiatrie . 2009; 77(1): 25–31 [English Abstract. Journal Article. Review].
- 21 Ngai S, Tang YM, Du L, et al. Hyperintensity of the middle cerebellar peduncles on fluid-attenuated inversion recovery imaging: variation with age and implications for the diagnosis of multiple system atrophy. Am J Neuroradiol 2006; 27(10): 2146–2148.
- 22 Simon JH, Kinkel RP, Jacobs L, et al. A Wallerian degeneration pattern in patients at risk for MS. Neurology 2000; 54(5): 1155–1160.
- 23 Misra UK, Kalita J, Das A. Vitamin B12 deficiency neurological syndromes: a clinical, MRI and electrodiagnostic study. Electromyogr Clin Neurophysiol 2003; 43(1): 57–64.
- 24 Matsuda K, Mihara T, Tottori T, et al. Neuroradiologic findings in focal cortical dysplasia: histologic correlation with surgically resected specimens. Epilepsia 2001; 42(Suppl 6): 29–36.
- 25 van Dijk EJ, Prins ND, Vrooman HA, et al. Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study. Stroke 2008; 39(10): 2712–2719.
- 26 Norrving B. Lacunar infarcts: no black holes in the brain are benign. Prac Neurol 2008; 8(4): 222–228.
- 27 Kitagawa K, Oku N, Kimura Y, et al. Relationship between cerebral blood flow and later cognitive decline in hypertensive patients with cerebral small vessel disease. Hypertension Res.–Clin. Exp. 2009; 32(9): 816–820.
- 28 Chen Y, Chen X, Xiao W, et al. Frontal lobe atrophy is associated with small vessel disease in ischemic stroke patients. Clin. Neurol. Neurosurg. 2009; 111(10): 852–857.
- 29 Assareh A, Mather KA, Schofield PR, et al. The genetics of white matter lesions. CNS Neurosci. Ther. 2011; 17(5): 525–540.
- 30 Putaala J, Kurkinen M, Tarvos V, et al. Silent brain infarcts and leukoaraiosis in young adults with first-ever ischemic stroke. Neurology 2009; 72(21): 1823–1829.
- 31 Ding XQ, Hagel C, Ringelstein EB, et al. MRI features of pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL). J. Neuroimag. 2010; 20(2): 134–140.
- 32 Fassbender K, Bertsch T, Mielke O, et al. Adhesion molecules in cerebrovascular diseases. Evidence for an inflammatory endothelial activation in cerebral large- and small-vessel disease. Stroke 1999; 30(8): 1647–1650.
- 33 Wada M, Nagasawa H, Kawanami T, et al. Cystatin C as an index of cerebral small vessel disease: results of a cross-sectional study in community-based Japanese elderly. Eur J Neurol 2010; 17(3): 383–390.
- 34 Fornage M, Chiang YA, O’Meara, E.S., et al. Biomarkers of inflammation and MRI-defined small vessel disease of the brain: the cardiovascular health study. Stroke 2008; 39(7): 1952–1959.
- 35 Wong A, Mok V, Fan YH, et al. Hyperhomocysteinemia is associated with volumetric white matter change in patients with small vessel disease. J Neurol 2006; 253(4): 441–447.
- 36 Kinney HC, Rava LA, Benowitz LI. Anatomic distribution of the growth-associated protein GAP 43 in developing human brainstem. J Neuropathol Exp Neurol 1993; 52(1): 39–54.
- 37 Shintani S, Tsuruoka S, Shiigai T. Pure sensory stroke caused by a cerebral hemorrhage: clinical-radiologic correlations in seven patients. Am J Neuroradiol . 2000; 21(3): 515–520.
- 38 Koyano S, Nagumo K, Niwa N, et al. [Disturbance of deep sensation in medial medullary syndrome. Topographical localization of medial lemniscus in the medulla oblongata]. [Review][30 refs][Japanese] Rinsho Shinkeigaku–Clin Neurol 1998; 38(8): 739–744.
- 39 Hagel J, Andrews G, Vertinsky T, et al. “Chasing the dragon”–imaging of heroin inhalation leukoencephalopathy. Can Assoc Radiol J 2005; 56(4): 199–203.
- 40 Lee SH, Kim DE, Song EC, et al. Sensory dermatomal representation in the medial lemniscus. Arch Neurol 2001; 58(4): 649–651.
- 41 Brown AG, Gordon G, Kay RH. A study of single axons in the cat's medial lemniscus. J Physiol 1974; 236(1): 225–246.
- 42 Rainey WT, Jones EG. Spatial distribution of individual medial lemniscal axons in the thalamic ventrobasal complex of the cat. Exp Brain Res 1983; 49(2): 229–246.
- 43 Feldman SG, Kruger L. An axonal transport study of the ascending projection of medial lemniscal neurons in the rat. J Comp Neurol 1980; 192(3): 427–454.
- 44 Galindo A, Krnjevic K, Schwartz S. Micro-iontophoretic studies on neurones in the cuneate nucleus. J Physiol 1967; 192(2): 359–377.
- 45 Angel RW, Goldstein M. Abnormal unloading reflex in a patient with infarction of the medial lemniscus. Ann Neurol 1983; 13(3): 279–284.
- 46 Marani E, Schoen JH. A reappraisal of the ascending systems in man, with emphasis on the medial lemniscus. Advances in Anatomy, Embryology & Cell Biology 2005; 179: 1–74.
- 47 Heckmann T, Bourassa CM. Lesions of the dorsal column nuclei or medial lemniscus of the cat: effect on motor performance. Brain Res 1981; 224(2): 405–411.
- 48 Benson RR, Guttmann CR, Wei X, et al. Older people with impaired mobility have specific loci of periventricular abnormality on MRI. Neurology 2002; 58: 48–55.
- 49 Rosano C, Kuller LH, Chung H, et al. Subclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults. J Am Geriatr Soc 2005; 53: 649–654.
- 50 Brun A, Englund E. A white matter disorder in dementia of the Alzheimer type: a pathoanatomical study. Ann Neurol 1986; 19: 253–262.
- 51 Baudrexel S, Nurnberger L, Rub U, et al. Quantitative mapping of T1 and T2* discloses nigral and brainstem pathology in early Parkinson's disease. Neuroimage 2010; 51(2): 512–520.
- 52 Meindl T, Wirth S, Weckbach S, et al. Magnetic resonance imaging of the cervical spine: comparison of 2D T2-weighted turbo spin echo, 2D T2*weighted gradient-recalled echo and 3D T2-weighted variable flip-angle turbo spin echo sequences. Eur Radiol 2009; 19: 713–721.
- 53 Saeed N, Hajnal JV, Oatridge A, et al. Regions of interest tracking in temporal scans based on statistical analysis of gray scale and edge properties and registration of images. J Magnetic Resonance Imaging 1998; 8: 182–187.
- 54 Shrout MK, Farley BA, Pratt SM, et al. The effect of region of interest variations on morphologic operations data and gray-level values extracted from digitized dental radiographs. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999; 88: 636–639.
- 55 White DR, Houston AS, Sampson WF, et al. Intra- and interoperator variations in region-of-interest drawing and their effect on the measurement of glomerular filtration rates. Clin Nucl Med 1999; 24(3): 177–181.
- 56 Hong JH, Son SM, Byun WM, et al. Aberrant pyramidal tract in medial lemniscus of brainstem in the human brain. Neuroreport 2009; 20(7): 695–697.
- 57 Yang DS, Hong JH, Byun WM, et al. Identification of the medial lemniscus in the human brain: combined study of functional MRI and diffusion tensor tractography. Neurosci Lett 2009; 459(1): 19–24.
- 58 Salamon N, Sicotte N, Alger J, Shattuck D, et al. Analysis of the brain-stem white-matter tracts with diffusion tensor imaging. Neuroradiology 2005; 47(12): 895–902.
Citing Literature
