Comparison of triple dose versus standard dose gadolinium-DTPA for detection of MRI enhancing lesions in patients with MS

We studied whether a triple dose of gadolinium-DTPA alone or in combination with delayed scanning increases the sensitivity of brain MRI for detecting enhancing lesions in patients with MS. We obtained T1-weighted brain MRI scans in two sessions for 22 patients with clinically definite MS. In the first session, we obtained one scan 5 to 7 minutes after the injection of 0.1 mmol/kg gadolinium-DTPA (standard dose). In the second session, 6 to 24 hours later, we obtained one scan before and two scans 5 to 7 minutes (for all patients) and one hour (for 11 patients) after the injection of 0.3 mmol/kg gadolinium-DTPA (triple dose). We detected 83 enhancing lesions in 14 patients when the standard dose of gadolinium-DTPA was used. The numbers of enhancing lesions increased to 138 (average increase 66%, p equals 0.001) and the numbers of patients with such lesions to 18 (increase 28%) when we used the triple dose of gadolinium-DTPA. In addition, the total area per patient occupied by such lesions was greater (p less than 0.0001) and lesion signal intensity higher (p equals 0.0001) on the triple-dose scans than the standard-dose scans. There was an increase in the number of large enhancing lesions (p equals 0.03) in the scans obtained 1 hour after the injection of the triple dose of gadolinium-DTPA. These data indicate that in patients with MS, a triple dose of gadolinium-DTPA can reveal many more enhancing lesions, which also appear larger. This suggests that the pathologic nature of ``active'' lesions in MS is heterogeneous, which might have impact on planning clinical trials. NEUROLOGY 1996;46: 379-384

[1]  W. Kaiser,et al.  Triple-dose versus standard-dose gadopentetate dimeglumine: a randomized study in 199 patients. , 1993, Radiology.

[2]  A. Thompson,et al.  Major differences in the dynamics of primary and secondary progressive multiple sclerosis , 1991, Annals of neurology.

[3]  A. Thompson,et al.  Magnetic resonance imaging in monitoring the treatment of multiple sclerosis: concerted action guidelines. , 1991, Journal of neurology, neurosurgery, and psychiatry.

[4]  R. Greene.  Fleischner Lecture. Imaging the respiratory system in the first few years after discovery of the X-ray: contributions of Francis H. Williams, M.D. , 1992, AJR. American journal of roentgenology.

[5]  D. N. Landon,et al.  Duration and selectivity of blood-brain barrier breakdown in chronic relapsing experimental allergic encephalomyelitis studied by gadolinium-DTPA and protein markers. , 1990, Brain : a journal of neurology.

[6]  J. Taubenberger,et al.  Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis , 1993, Annals of neurology.

[7]  B E Kendall,et al.  Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. , 1990, Brain : a journal of neurology.

[8]  F. Barkhof,et al.  Gadolinium enhancement increases the sensitivity of MRI in detecting disease activity in multiple sclerosis. , 1993, Brain : a journal of neurology.

[9]  H. McFarland,et al.  Clinical worsening in multiple sclerosis is associated with increased frequency and area of gadopentetate dimeglumine–enhancing magnetic resonance imaging lesions , 1993, Annals of neurology.

[10]  G. C. Hurst,et al.  Improved contrast of enhancing brain lesions on postgadolinium, T1-weighted spin-echo images with use of magnetization transfer. , 1994, Radiology.

[11]  W. Mcdonald,et al.  The pathological evolution of multiple sclerosis , 1992, Neuropathology and applied neurobiology.

[12]  D. Schiffer,et al.  Age‐related ubiquitin deposits in dystrophic neurites: an immunoelectron microscopic study , 1992, Neuropathology and applied neurobiology.

[13]  J. Ebersole,et al.  An evaluation of ambulatory, cassette EEG monitoring , 1983, Neurology.

[14]  Karl J. Friston,et al.  Functional mapping of brain areas implicated in auditory--verbal memory function. , 1993, Brain : a journal of neurology.

[15]  R. Kikinis,et al.  Longitudinal MRI in multiple sclerosis , 1994, Neurology.

[16]  P. Ell,et al.  99TCm-HMPAO SPECT studies in traumatic intracerebral haematoma. , 1991, Journal of neurology, neurosurgery, and psychiatry.

[17]  V. Runge,et al.  High‐dose applications of gadolinium chelates in magnetic resonance imaging , 1991, Magnetic resonance in medicine.

[18]  A. Thompson,et al.  Benign form of multiple sclerosis: MRI evidence for less frequent and less inflammatory disease activity. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[19]  A. Thompson,et al.  Magnetic resonance imaging in monitoring the treatment of multiple sclerosis patients: Statistical power of parallel-groups and crossover designs , 1994, Journal of the Neurological Sciences.

[20]  V. Runge,et al.  High‐dose gadoteridol in MR imaging of intracranial neoplasms , 1992, Journal of magnetic resonance imaging : JMRI.

[21]  D. Miller,et al.  Magnetic resonance in monitoring the treatment of multiple sclerosis , 1994, Annals of neurology.

[22]  W. Koller.  How accurately can Parkinson's disease be diagnosed? , 1992, Neurology.

[23]  J. Parisi,et al.  Neurological involvement in Wegener's granulomatosis: An analysis of 324 consecutive patients at the Mayo Clinic , 1993, Annals of neurology.

[24]  A. Thompson,et al.  Serial gadolinium‐enhanced MRI in relapsing/remitting multiple sclerosis of varying disease duration , 1992, Neurology.

[25]  A. Fox,et al.  New perspectives in computed tomography of multiple sclerosis. , 1982, AJR. American journal of roentgenology.

[26]  L. Hayman,et al.  Maximizing the harvest of contrast enhancing lesions in multiple sclerosis , 1982, Neurology.

[27]  S. Cook,et al.  Triple‐Dose Versus Single‐Dose Gadoteridol in Multiple Sclerosis Patients , 1994, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[28]  W. I. McDonald,et al.  Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis , 1994, Neurology.

[29]  W. Mcdonald,et al.  Patterns of blood-brain barrier breakdown in inflammatory demyelination. , 1991, Brain : a journal of neurology.

[30]  B E Kendall,et al.  Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis. , 1988, Brain : a journal of neurology.

[31]  W. I. McDonald,et al.  Heterogeneity of blood‐brain barrier changes in multiple sclerosis , 1990, Neurology.

[32]  D. Pelz,et al.  CT of multiple sclerosis: reassessment of delayed scanning with high doses of contrast material. , 1985, AJR. American journal of roentgenology.

[33]  F. Barkhof,et al.  Relapsing-remitting multiple sclerosis: sequential enhanced MR imaging vs clinical findings in determining disease activity. , 1992, AJR. American journal of roentgenology.

[34]  D. Miller,et al.  Are magnetic resonance findings predictive of clinical outcome in therapeutic trials in multiple sclerosis? The dilemma of interferon‐β , 1994, Annals of neurology.

[35]  J. Kurtzke.  Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[36]  J. Ehrhardt,et al.  Review of the use of high-dose gadoteridol in the magnetic resonance evaluation of central nervous system tumors. , 1992, Investigative radiology.

[37]  N. Patronas,et al.  Serial gadolinium‐enhanced magnetic resonance imaging scans in patients with early, relapsing‐remitting multiple sclerosis: Implications for clinical trials and natural history , 1991, Annals of neurology.

[38]  V. Haughton,et al.  Cranial tissues: normal MR appearance after intravenous injection of Gd-DTPA. , 1986, Radiology.