Pr F. Cotton

Imaging department

The imaging department at Lyon Sud hospital is a very active multi-purpose service (more than 117,000 procedures per year, including 45,000 medical procedures), focused on oncology, screening, diagnosis and interventional imaging.

neuro-ophtamologie
Pr-Claire-Haegelen

Research axis

Imaging of multiple sclerosis and inflammatory diseases of the brain and spinal cord. Head of the imaging group at the French Multiple Sclerosis Observatory. Publication of recommendations on the diagnosis and MRI monitoring of patients with MS. Organization of three international challenges on OFSEP MRI data (MICCAI 2016 and 2021, JFR 2019)

  • Imaging of normal and pathological brain aging.
  • Doctoral thesis subject. Responsible for the imaging group on MEMORA.
  • Imaging of disability and cerebral plasticity, with MPR teams Multimodal imaging in neurooncology Cranial nerve tractography, Neuroanatomy

Links with teams

  • Nationals with INRIA team at Rennes and CREATIS, Team 5
  • Internationals since 1997 with Pr Charles Gutmmann team at Haravd Medical School, Boston, MA, USA
  • Dr Salem Hannoun, Berouth, Liban
  • Pr. Oroth Rasphone, Hopital Mahosot et Dr Viengkham Leuangvanxay, hôpital de l’amitié, Vientiane, Laos

Publications

1. MRI of central nervous system in a series of 58 systemic lupus erythematosus (SLE) patients with or without overt neuropsychiatric manifestations. Revue de Médecine Interne 2004; 25(1): 8-15.

Cotton F, Bouffard-Vercelli J, Hermier M, Tebib J, Vital Durand D, Tran Minh VA, Rousset H.

[MRI of central nervous system in a series of 58 systemic lupus erythematosus (SLE) patients with or without overt neuropsychiatric manifestations] — Résumé

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Purpose: Central nervous (CNS) involvement in SLE is common and can be evaluated with MRI. The primary goal of this study was to evaluate with high-field MRI the CNS involvement in a series of SLE patients with or without neuropsychiatric symptoms. The secondary goal was to detect a possible relationship between MRI and clinical or biological parameters in SLE.

Materials and methods: We correlated the clinical and biological parameters of 58 patients with a lupus defined according to the American College of Rheumatology criteria, including 30 with neuropsychiatric manifestations with conventional and modern MRI (including diffusion weighted-images, high-resolution 3D T1 weighted-images). The population studied was compared to a group of 18 normal controls.

Results: In 69% of cases, MRI demonstrated involvement of the CNS both in asymptomatic patients (64.3%) and in patients with neuropsychiatric manifestations (73.3%): microembolic signals, cerebral infarctions (associated with the anti-phospholipid syndrome), atrophy, basal ganglia involvement, posterior leucoencephalopathy, subcortical calcification or hemosiderin deposits (T2*), dilated perivascular spaces.

Conclusion: MRI with adapted sequences clearly demonstrated the cerebral involvement in approximately 70% of SLE patients with or without neuropsychiatric symptoms.

2. Cranial sutures and craniometric points detected on MRI.
Surgical and Radiologic Anatomy 2005; 27(1): 64-70.

Cotton F, Rozzi FR, Vallée B, Pachai C, Hermier M, Guihard-Costa AM, Froment JC.

Cranial sutures and craniometric points detected on MRI — Résumé

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The main goal of the study was to determine on MRI the cranial sutures, the craniometric points and craniometric measurements, and to correlate these results with classical anthropometric measurements. For this purpose, we reviewed 150 cerebral MRI examinations considered as normal (Caucasian population aged 20-49 years). For each examination we individualized 11 craniometric landmarks (Glabella, Bregma, Lambda, Opisthocranion, Opisthion, Basion, Inion, Porion, Infra-orbital, Eurion) and three measurements. Measurements were also calculated independently on 498 dry crania (Microscribe 3-DX digitizer). To validate the MRI procedure, we measured four dry crania by MRI and with compass or digital caliper gauges. Cranial sutures always appeared without signal (black), whatever the MRI sequence used, and they are better visualized with a 5 mm slice thickness (compact bone overlapping). Slice dynamic analysis and multiplanar reformatting allowed the detection of all craniometric points, some of these being more difficult to detect than others (Porion, Infra-orbital). The measurements determined by these points were as follows: Vertex-Basion height=135.66+/-6.56 mm; Eurion-Eurion width=141.17+/-5.19 mm; Glabella-Opisthocranion length=181.94+/-6.40 mm. On the midline T1-weighted sagittal image, all median craniometric landmarks can be individualized and the Glabella-Opisthocranion length, Vertex-Basion height and parenchyma indices can be calculated. Craniometric points and measurements between these points can be estimated with a standard cerebral MRI examination, with results that are similar to anthropometric data.

3. IRM de diffusion-perfusion dans l’évaluation des lymphomes cérébraux. J Neuroradiol. 2006; 33: 220-228.

Cotton F, Ongolo-Zogo P, Louis-Tisserand G, Streichenberger N, Hermier M, Jouvet A, Hlaihel C, Jouanneau E, Salles G, Froment JC.

IRM de diffusion-perfusion dans l’évaluation des lymphomes cérébraux — Résumé

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En raison de l’augmentation de l’incidence des lymphomes cérébraux (LC), il est utile de maîtriser la séméiologie IRM de cette entité pathologique potentiellement curable. Nous présentons une analyse rétrospective de 9 patients porteurs de 13 lésions de LC histologiquement prouvés et une revue de la littérature sur les aspects IRM morphologiques et de diffusion-perfusion des LC. Tous les patients ont été explorés par des séquences morphologiques avant et après injection de chélates de gadolinium. L’IRM de diffusion a été effectuée à l’aide d’une séquence Echo Planar Single Shot avec génération automatisée du coefficient de diffusion apparent (CDA). L’IRM de perfusion a été effectuée à l’aide d’une séquence Écho Planar de type Écho de Gradient en pondération T2* après injection intraveineuse d’un bolus de gadolinium avec un débit de 6 ml/s et une résolution temporelle de 1 seconde. Les données IRM morphologiques, de diffusion avec calcul du CDA moyen de la tumeur et de la substance blanche normale, et de perfusion avec calcul du volume sanguin cérébral relatif maximal (VSCrmax) de la tumeur et aspect de la courbe de perfusion, ont été analysées.

Sur le plan morphologique, le LC était toujours iso ou hypointense en T1 et iso-intense ou hypointense en T2 par rapport à la substance grise dans 75 % des cas Toutes les lésions sauf une (patient sous corticothérapie) prenaient le contraste. Sur les séquences pondérées en diffusion, les 13 lésions étaient en hypersignal. Le CDA tumoral moyen était égal à 0,717 ± 0,152.10–3 mm2/sec (0,550-1,014). Le ratio CDA tumoral/CDA substance blanche était égal à 0,974 ± 0,190 (0,768-1,410). Toutes les courbes de perfusion tumorale présentaient un aspect caractéristique de remontée importante au dessus de la ligne de base après le premier passage. Le VSCrmax moyen des lésions était égal à 1,43 ± 0,64 (0,55-2,62).

De part leur leurs forte cellularité, l’absence de néo vascularisation et la rupture de la barrière hématoencéphalique par l’infiltration des parois capillaires par les cellules lymphomateuses, les LC présentent une séméiologie particulière en IRM de diffusion-perfusion dont la connaissance devrait en améliorer le diagnostic et le suivi.

Diffusion and perfusion MR imaging in cerebral lymphomas

Because of the increasing incidence of cerebral lymphoma, it is critical for patient management to recognize the MR features of this disease. We present the characteristic morphological and functional MRI features of this tumor. The findings on MRI studies, including morphological, diffusion and perfusion imaging, performed in 9 biopsy-proven cases of cerebral lymphoma with 13 lesions are presented and analyzed, and are discussed in comparison with published literature data. All patients underwent diffusion-weighted imaging with a single shot echo-planar pulse sequence. Dynamic susceptibility-contrast MRI was performed using a T2*-weighted gradient-echo echo-planar sequence after intravenous injection of chelates of gadolinium at the rate of 6 ml/s and a temporal resolution of 1 second.

All cases of cerebral lymphoma appeared hypointense or isointense on T1-weighted images and in 75% of cases iso- or hypointense on T2-weighted images. All lesions enhanced except one in a patient receiving steroid therapy. On diffusion-weighted images, tumours were hyperintense with normal or decreased ADC values (0.717±0.152.10–3 mm2/sec, range: 0.550-1.014) and an ADC ratio tumour/normal white matter of 0.974±0.190 (range: 0.768-1.410). On perfusion, the signal intensity-time curve of each tumour showed a characteristic type of curve with a significant increase of the signal intensity above the baseline and a low maximum relative cerebral blood volume ratio (rCVBmax) of 1.43±0.64 (0.55-2.62).

Due to their higher cellularity, the lack of neoangiogenesis, and the increased permeability of the blood-brain barrier related to the infiltration of blood vessels wall by lymphomatous cells, cerebral lymphoma presents characteristic diffusion and perfusion MRI features that should be useful for diagnosis and patient follow-up.

Mots clés : IRM , perfusion , tumeur cérébrale , lymphome

Keywords: Magnetic Resonance Imaging , perfusion , brain neoplasms , lymphoma

4. Could linear MRI measurements of hippocampus differentiate normal brain aging in elderly persons from
Alzheimer disease? Surgical and Radiologic Anatomy 2007; 29: 77-81.

Tarroun A, Bonnefoy M, Bouffard-Vercelli J, Gedeon C, Vallee B, Cotton F.

Could linear MRI measurements of hippocampus differentiate normal brain aging in elderly persons from Alzheimer disease? — Résumé

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Although mild progressive specific structural brain changes are commonly associated with normal human aging, it is unclear whether automatic or manual measurements of these structures can differentiate normal brain aging in elderly persons from patients suffering from cognitive impairment. The objective of this study was primarily to define, with a standard high resolution MRI, the range of normal linear age-specific values for the hippocampal formation (HF), and secondarily to differentiate hippocampal atrophy in normal aging from that occurring in Alzheimer disease (AD). Two MRI-based linear measurements of the hippocampal formation at the level of the head and of the tail, standardized by the cranial dimensions, were obtained from coronal and sagittal T1-weighted MR images in 25 normal elderly subjects, and 26 patients with AD. In this study, dimensions of the HF have been standardized and they revealed normal distributions for each side and each sex: the width of the hippocampal head at the level of the amygdala was 16.42 +/- 1.9 mm, and its height 7.93 +/- 1.4 mm; the width of the tail at the level of the cerebral aqueduct was 8.54 +/- 1.2 mm, and the height 5.74 +/- 0.4 mm. There were no significant differences in standardized dimensions of the HF between sides, sexes, or in comparison to head dimensions in the two groups. In addition, the median inter-observer agreement index was 93%. In contrast, the dimensions of the hippocampal formation decreased gradually with increasing age, owing to physiological atrophy, but this atrophy is more significant in the group of AD.

5. MRI contrast uptake in new lesions in relapsing-remitting MS followed at weekly intervals. Neurology 2003; 60: 640-646.

Cotton F, Weiner HL, Jolesz FA, Guttmann Charles.

MRI contrast uptake in new lesions in relapsing-remitting MS followed at weekly intervals - PubMed — Résumé

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Background: One of the diagnostic imaging hallmarks of MS is the uptake of IV administered contrast material in new lesions in the brain, signaling blood-brain barrier breakdown and active inflammation. Many clinical drug trials are designed based on the assumption that lesion enhancement on MRI remains visible on average for 1 month. For practical reasons, few serial MRI studies of patients with MS have been performed at intervals shorter than 4 weeks.

Methods: The authors performed a year-long longitudinal study in 26 patients with relapsing-remitting MS (RRMS), which comprised an initial phase of MRI follow-up at weekly intervals for 8 weeks, followed by imaging every other week for another 16 weeks, and monthly thereafter. They present a quantitative analysis (using a supervised interactive thresholding procedure) of new enhancing lesions appearing during the first 6 weeks in this cohort and evaluated from the time of first detection until enhancement was no longer seen.

Results: The average duration of Gd-DTPA enhancement in individual new lesions was 3.07 weeks (median, 2 weeks). Significant correlations were demonstrated between the duration of contrast enhancement or initial growth rates and lesion volumes. Different lesions in the same patient appeared to develop largely independent of each other and demonstrated a large range in the duration of enhancement during the acute phase of their evolution.

Conclusions: The average duration of blood-brain barrier impairment in RRMS is shorter than earlier estimates. Early lesion growth parameters may predict final lesion size. Within-patient heterogeneity of lesion evolution suggests that individual lesions develop independently.

6. Optic ataxia errors depend on remapped, not viewed, target location. Nature Neuroscience 2005; 8(4): 418-420.

Khan AZ, Pisella L, Vighetto A, Cotton F, Luaute J, Boisson D, Salemme R, Crawford JD, Rossetti Y.

Optic ataxia errors depend on remapped, not viewed, target location — Résumé

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Optic ataxia is a disorder associated with posterior parietal lobe lesions, in which visually guided reaching errors typically occur for peripheral targets. It has been assumed that these errors are related to a faulty sensorimotor transformation of inputs from the ‘ataxic visual field’. However, we show here that the errors observed in the contralesional field in optic ataxia depend on a dynamic gaze-centered internal representation of reach space.

7. Diffusion- weighted magnetic resonance imaging in Marchiafava-Bignami disease: follow-up studies. Neuroradiology 2005; 47(7): 520-524.

Hlaihel C, Gonnaud PM, Champin S, Rousset H, Tran Minh VA, Cotton F.

Diffusion-weighted magnetic resonance imaging in Marchiafava-Bignami disease: — Résumé

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Marchiafava-Bignami disease (MBD), an acute toxic demyelination of the corpus callosum in alcoholics, is associated with poor evolution in the majority of patients. We report here the early and late diffusion magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) studies of two patients suffering from MBD with favourable outcome. Diffusion and anatomical MRI changes were parallel to the clinical evolution, suggesting that MRI studies can be helpful for diagnosis and follow-up. Unlike in stroke, restricted diffusion on ADC maps does not seem to be a sign of irreversibility.

8. Correlation between cranial vault size and brain size over time: preliminary MRI evaluation. Journal of Neuroradiology 2005; 32(2): 131-137.

Cotton F, Euvrard T, Durand-Dubief F, Pachai C, Cucherat M, Ramirez Rozzi F, Bonmartin A, Guihard-Costa AM, Tran Minh VA, Vallée B, Froment JC.

[Correlation between cranial vault size and brain size over time: preliminary MRI evaluation] — Résumé

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Objectives: To correlate changes of cranial vault measurements of an adult population during the aging process with brain size using the maximum width of the third ventricle in the axial AC-PC plane.

Materials and methods: Prospective study of 126 adult subjects (range: 20 to 80 years) with normal brain MRI and without history of neuropsychiatric disorder. MEASUREMENTS INCLUDED: Cranial vault (Maximum length: Glabella-Opisthocranion, Maximum width: euryon-euryon, and maximum height: Basion-Vertex) measurements and maximum width of the third ventricle in the A C-PC plane.

Results: Vault measurements (length, width, high) were similar for every age group, irrespective of gender. The variability of cranial vault measurements between individuals was low (<1 cm). Cranial vault measurements were larger for men, but this was not significant when adjusted for body height Comparatively, a gradual widening of the third ventricle, with an exponential behavior, was observed with advancing age.

Conclusion: Our results indicate that cranial vault measurements are stable over time (between 20-80 years) comparatively to brain atrophy with advancing age. The low variability of cranial vault measurements and their stability over time should be taken into account during segmentation and normalization of brain parenchymal structures.

9. Relevant usage of diffusion and perfusion MR Imaging for the evaluation of intra-axial brain
tumors in clinical routine-

Rollin N, Guyotat J, Streichenberger N, Honnorat J, Tran Minh VA, Cotton F. Neuroradiology, 2006; 48: 150-159.

Clinical relevance of diffusion and perfusion magnetic resonance imaging in assessing intra-axial brain tumors — Résumé

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Advanced magnetic resonance (MR) imaging techniques provide physiologic information that complements the anatomic information available from conventional MR imaging. We evaluated the roles of diffusion and perfusion imaging for the assessment of grade and type of histologically proven intraaxial brain tumors. A total of 28 patients with intraaxial brain tumors underwent conventional MR imaging (T2- and T1-weighted sequences after gadobenate dimeglumine injection), diffusion imaging and T2*-weighted echo-planar perfusion imaging. Examinations were performed on 19 patients during initial diagnosis and on nine patients during follow-up therapy. Determinations of relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were performed in the solid parts of each tumor, peritumoral region and contralateral white matter. For gliomas, rCBV values were greater in high-grade than in low-grade tumors (3.87+/-1.94 versus 1.30+/-0.42) at the time of initial diagnosis. rCBV values were increased in all recurrent tumors, except in one patient who presented with a combination of recurrent glioblastoma and massive radionecrosis on histology. Low-grade gliomas had low rCBV even in the presence of contrast medium enhancement. Differentiation between high- and low-grade gliomas was not possible using diffusion-weighted images and ADC values alone. In the peritumoral areas of untreated high-grade gliomas and metastases, the mean rCBV values were higher for high-grade gliomas (1.7+/-0.37) than for metastases (0.54+/-0.18) while the mean ADC values were higher for metastases. The rCBV values of four lymphomas were low and the signal intensity-time curves revealed a significant increase in signal intensity after the first pass of gadobenate dimeglumine. Diffusion and perfusion imaging, even with relatively short imaging and data processing times, provide important information for lesion characterization.

10. Predictive value of multimodality MRI using conventional, perfusion, and spectroscopy MR in anaplastic
transformation of low-grade oligodendrogliomas. J Neurooncol. 2010;97(1):73-80.

Hlaihel C, Guilloton L, Guyotat J, Streichenberger N, Honnorat J, Cotton F.

Predictive value of multimodality MRI using conventional, perfusion, and spectroscopy MR in anaplastic transformation of low-grade oligodendrogliomas — Résumé

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The aim of our study was to evaluate the role of proton magnetic resonance (MR) spectroscopy and MR perfusion in the follow-up of low-grade gliomas, since conventional MR imaging (MRI) is not reliable in detecting the passage from a low- to high-grade tumor. Twenty-one patients with a World Health Organisation (WHO) grade II glioma were followed up using proton MR spectroscopy, perfusion, and conventional MRIs. Follow-up MRIs had been performed at the third month of evolution and then twice a year, with an average of five MR studies per patient. Five out of the 21 patients had an anaplastic transformation. A choline to creatine ratio (choline/creatine ratio) above 2.4 is associated with an 83% risk of a malignant transformation in an average delay of 15.4 months. The choline/creatine ratio at this threshold was more efficient than perfusion MR in detecting the anaplastic transformation, with sensitivity of 80% and specificity of 94%. An increased choline/creatine ratio seemed to occur an average 15 months before the elevation of relative cerebral blood volume (rCBV). The mean annual growth of low-grade glioma was 3.65 mm. A growth rate higher than 3 mm per year was also correlated with greater risk of anaplastic transformation. Proton magnetic resonance spectroscopy should be recommended in the follow-up of low-grade gliomas since the choline/creatine ratio can predict anaplastic transformation before perfusion abnormalities, with high positive predictive value of 83%.