How stereological analysis of vascular morphology can quantify the blood volume fraction as a marker for tumor vasculature: comparison with magnetic resonance imaging

To assess angiogenesis noninvasively in a C6 rat brain tumor model, the rapid-steady-state-T(1) (RSST(1)) magnetic resonance imaging (MRI) method was used for microvascular blood volume fraction (BVf) quantification with a novel contrast agent gadolinium per (3,6 anhydro) α-cyclodextrin (Gd-ACX). In brain tissue contralateral to the tumor, equal BVfs were obtained with Gd-ACX and the clinically approved gadoterate meglumine (Gd-DOTA). Contrary to Gd-DOTA, which leaks out of the tumor vasculature, Gd-ACX was shown to remain vascular in the tumor tissue allowing quantification of the tumor BVf. We sought to confirm the obtained tumor BVf using an independent method: instead of using a 'standard' two-dimensional histologic method, we study here how vascular morphometry combined with a stereological technique can be used for three-dimensional assessment of the vascular volume fraction (V(V)). The V(V) is calculated from the vascular diameter and length density. First, the technique is evaluated on simulated data and the healthy rat brain vasculature and is then applied to the same C6 tumor vasculature previously quantified by RSST(1)-MRI with Gd-ACX. The mean perfused V(V) and the BVf obtained by MRI in tumor regions are practically equal and the technique confirms the spatial heterogeneity revealed by MRI.     

In vivo quantification of spinal and bulbar motor neuron degeneration in the G93A-SOD1 transgenic mouse model of ALS by T2 relaxation time and apparent diffusion coefficient

Magnetic resonance imaging (MRI) has provided important information in characterizing amyotrophic lateral sclerosis (ALS) in humans and in animal models. A frequently used animal model to study mechanisms of pathogenesis and the efficacy of drugs in ALS is a transgenic mouse over-expressing the human mutated G93A-superoxide dismutase 1 (G93A-SOD1). In our study, we applied MRI to find suitable progression markers, which can be used to monitor the development of ALS and to evaluate therapeutic approaches at early stages of the disease. Therefore, we generated parameter maps of the spin-spin relaxation time (T2) and the apparent diffusion coefficient (ADC) starting at day 70 after birth, i.e., before motor scores decline around day 90. Depending on the progression of the disease, G93A-SOD1 mice showed significantly increased values of T2 in the brain stem motor nuclei Nc. V (trigeminal nucleus), VII (facial nucleus), and XII (hypoglossal nucleus), and spinal cord compared to non-transgenic wild-type mice and transgenic mice over-expressing the non-mutated wild-type human SOD1 (tg-SOD1). Similar effects in these motor nuclei were revealed by ADC mapping. Furthermore, in the upper spinal cord, a dorsal-ventral difference with significantly higher T2 values in the ventral part was demonstrated by T2 mapping. While both T2 and ADC might prove useful as progression markers and enable the longitudinal non-invasive evaluation of ALS in G93A-SOD1 mice, the potential is limited by age-dependent effects in case of ADC mapping.     

Cerebral fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomography (FDG PET), MRI, and clinical observations in a patient with infantile GM1 gangliosidosis

The clinical, biochemical, pathological and neuroradiological findings of a 2-year-old Saudi boy with infantile G_M1 gangliosidosis are reported. The patient had a progressive neurologic deterioration, manifesting with developmental regression, sensorimotor and psychointellectual dysfunction and generalized spasticity that started at 4 months of age. Cherry-red macula, facial dysmorphia, hepatomegaly, exaggerated startle response to sounds, skeletal dysplasia, and vacuolated foamy lymphocytes that contain finely fibrillar material in addition to lamellar membranes and electron-dense rounded bodies were seen. MRI of the brain demonstrated mild diffuse brain atrophy and features of delayed dysmyelination and demyelination. Brain FDG PET scan revealed a mild decrease in the basal ganglia uptake, and moderate to severe decrease in thalamic and visual cortex uptake, and an area of increased glucose uptake in the left frontal lobe, probably representing an active seizure focus. The functional changes indicated by FDG PET scan and the structural abnormalities shown on MRI were found to be complementary in the imaging evaluation of infantile G_M1 gangliosidosis.     

Dopamine D1 receptor number — a sensitive PET marker for early brain degeneration in Huntington's disease

Summary D₁-dopamine receptor binding in the brain was determined by positron emission tomography (PET) in five patients with Huntington's disease, in one asymptomatic gene carrier and in five control subjects. [¹¹C] SCH 23390 was used as the radioligand. Brain morphology was recorded by MRI. The patients who all had a mild to moderate functional impairment showed an almost 50% reduction of putamen volume as well as D₁-dopamine receptor density as compared to the controls. The total D₁-dopamine receptor number in the putamen was reduced by 75% in the patient group. A similar reduction was found for the caudate nucleus. The asymptomatic gene carrier had volume and density values in the lower range of the control subjects. In the frontal neocortex there also tended to be a reduced D₁-dopamine receptor binding in the symptomatic patients. The results indicate that [¹¹C] SCH 23390 binding in combination with MRI can be used as a sensitive marker for early brain degeneration in Huntington's disease. This marker may be useful to monitor the pathophysiological effect of the disease gene and also to follow therapeutic interventions aiming at preventing the degenerative process.     

New Opportunities for High-Field In Vivo MRS in Studying Brain Bioenergetics and Function

In general, the methodology of magnetic resonance applied in brain research can be divided into two categories: magnetic resonance imaging (MRI) and spectroscopy (MRS). MRI provides rich contrast which is useful for studying brain anatomy, function, behavior and disease. The great merit of in vivo MRS is its ability for noninvasively measuring a variety of cerebral metabolites and neurotransmitters inside a brain. It, therefore, provides an invaluable tool for determining metabolites, chemical reaction rates and bioenergetics, as well as their changes in the human and animal brains. The capability of in vivo MRS is further enhanced at high/ultrahigh magnetic fields because of significant improvements in the detection sensitivity and spectral resolution. Recent progress in technology development has further demonstrated the great potential and promise of in vivo MRS, particularly, in brain research. This article provides a brief review of in vivo MRS methodologies and their applications for determining the cerebral metabolic rates of oxygen, glucose and ATP noninvasively.     

Microscopic Visualization of Metabotropic Glutamate Receptors on the Surface of Living Cells Using Bifunctional Magnetic Resonance Imaging Probes

相似文献   

Cerebrovascular reactivity in the brain white matter: magnitude,temporal characteristics,and age effects

White matter (WM) comprises about half of the brain and its dysfunction is implicated in many brain disorders. While structural properties in healthy and diseased WM have been extensively studied, relatively little is known about the physiology underlying these structural characteristics. Recent advances in magnetic resonance (MR) technologies provided new opportunities to better understand perfusion and microvasculature in the WM. Here, we aim to evaluate vasodilatory capacity of the WM vasculature, which is thought to be important in tissue ischemia and autoregulation. Fifteen younger and fifteen older subjects performed a CO₂ inhalation task while blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging (MRI) images were continuously collected. The cerebrovascular reactivity (CVR) index showed that the value of CVR in the WM (0.03±0.002%/mm Hg) was positive, but was significantly lower than that in the gray matter (GM) (0.22±0.01%/mm Hg). More strikingly, the WM response showed a temporal delay of 19±3 seconds compared with GM, which was attributed to the longer time it takes for extravascular CO₂ to change. With age, WM CVR response becomes greater and faster, which is opposite to the changes seen in the GM. These data suggest that characteristics of WM CVR are different from that of GM and caution should be used when interpreting pathologic WM CVR results.     

Investigating the Medial Temporal Lobe in Alzheimer’s Disease and Mild Cognitive Impairment, with Turboprop Diffusion Tensor Imaging, MRI-volumetry, and T 2-relaxometry

The first neuropathological alterations in Alzheimer’s disease (AD) occur in the medial temporal lobes (MTLs), in the entorhinal cortex (EC), perforant pathway (PP), and hippocampus. The purpose of this study was to investigate the microstructural integrity, size, and T ₂-relaxation times of MTL structures in patients with AD and mild cognitive impairment (MCI), using MRI techniques that are immune to magnetic field inhomogeneities. Turboprop-DTI and high-resolution anatomical MRI data were obtained on AD and MCI patients, and healthy controls. Significant AD-related changes were detected in more MTL structures of AD patients by means of Turboprop-DTI than with any other technique used. Mean diffusivity and T ₂-relaxation times of specific MTL structures increased in both the MCI and AD cohorts when compared to normal controls. Therefore, Turboprop-DTI and T ₂-relaxometry may be valuable non-invasive tools in the investigation of the early AD-related neuropathological alterations.     

Face memory in MRI-positive and MRI-negative temporal lobe epilepsy

PURPOSE: Effects of MRI-positive (MRI(+)) as compared to MRI-negative (MRI(-)) temporal lobe epilepsy (TLE) on face memory are not yet known. METHODS: We studied 24 MRI(-) (11 right/13 left) and 20 MRI(+) (13 right/7 left) TLE patients, 12 generalized epilepsy patients, and 12 healthy subjects undergoing diagnostic workup with 24-72-h Video-EEG-monitoring. Twenty faces were shown, and had to be recognized from 40 faces immediately and after a 24-h delay. RESULTS: MRI(+) and MRI(-) right TLE (RTLE) patients showed deficits in face recognition compared to controls or generalized epilepsy, consistent with right temporal lobe dominance for face recognition. MRI(+) RTLE patients had deficits in both immediate and delayed recognition, while MRI(-) RTLE patients showed delayed recognition deficits only. The RTLE groups showed comparable delayed recognition deficits. Separate analyses in which the MRI(+) group included patients with hippocampal sclerosis only, did not alter results. Furthermore, MRI(-) RTLE had a worse delayed recognition than MRI(-) left TLE (LTLE). On the other hand, MRI(+) RTLE did not differ from MRI(+) LTLE in delayed recognition. Combining MRI(-) and MRI(+) TLE groups, we found differences between RTLE and LTLE in delayed, but not immediate face recognition. CONCLUSIONS: Our results suggest that a delayed recognition condition might be superior to immediate recognition tests in detecting face memory deficits in MRI(-) RTLE patients. This might explain why former studies in preoperative patients did not observe an immediate face recognition dominance of the right temporal lobe when combining MRI(-) and MRI(+) TLE patients. Our data further point to an important role of the right mesial temporal region in face recognition in TLE.     

DHA and cholesterol containing diets influence Alzheimer-like pathology, cognition and cerebral vasculature in APPswe/PS1dE9 mice

Cholesterol and docosahexenoic acid (DHA) may affect degenerative processes in Alzheimer's Disease (AD) by influencing Aβ metabolism indirectly via the vasculature. We investigated whether DHA-enriched diets or cholesterol-containing Typical Western Diets (TWD) alter behavior and cognition, cerebral hemodynamics (relative cerebral blood volume (rCBV)) and Aβ deposition in 8- and 15-month-old APP_swe/PS1_dE9 mice. In addition we investigated whether changes in rCBV precede changes in Aβ deposition or vice versa. Mice were fed regular rodent chow, a TWD-, or a DHA-containing diet. Behavior, learning and memory were investigated, and rCBV was measured using contrast-enhanced MRI. The Aβ load was visualized immunohistochemically. We demonstrate that DHA altered rCBV in 8-month-old APP/PS1 and wild type mice[AU1]. In 15-month-old APP/PS1 mice DHA supplementation improved spatial memory, decreased Aβ deposition and slightly increased rCBV, indicating that a DHA-enriched diet can diminish AD-like pathology. In contrast, TWD diets decreased rCBV in 15-month-old mice. The present data indicate that long-term dietary interventions change AD-like pathology in APP/PS1 mice. Additionally, effects of the tested diets on vascular parameters were observed before effects on Aβ load were noted. These data underline the importance of vascular factors in the APP/PS1 mouse model of AD pathology.     

Parenchymal brain injury in the preterm infant: comparison of cranial ultrasound, MRI and neurodevelopmental outcome

AIM: Magnetic resonance imaging (MRI) is increasingly being used in high-risk preterm neonates. Cranial ultrasound (US) was compared with MRI in preterm patients with parenchymal injury and related to neurodevelopmental outcome. PATIENTS AND METHODS: Studies were performed in 61 patients. Twelve infants with normal US (Group 1) had an MRI within the first 4 weeks of life (early MRI), and 10 also at term age (late MRI). Eight out of 20 infants with intraventricular haemorrhage with parenchymal involvement (IVH + PI) (Group 2) had an early as well as a late MRI and 12 a late MRI. Of the 20 patients with cystic-periventricular leukomalacia (c-PVL) (Group 3), 7 had an early MRI, 1 had an MRI on both occasions and 12 had a late MRI. All 9 children with focal infarction (FI) (Group 4) had a late MRI. RESULTS: MRI was conform with cranial US in Group 1. Early MRI in Group 2 showed contralateral c-PVL in one infant and an additional contralateral occipital parenchymal haemorrhage and blood in the posterior fossa in another infant. Late MRI showed an asymmetrical posterior limb of the internal capsule (PLIC) (n=6), which predicted later hemiplegia. Early MRI in Group 3 showed more cysts (n = 5), punctate white matter lesions (n = 6), lesions in the basal ganglia (n = 1) and once involvement of the cerebellum. Late MRI showed involvement of the centrum semiovale (n = 2) lesions in the basal ganglia (n = 2) and bilateral abnormal signal intensity of the PLIC in 7 infants who all went on to develop cerebral palsy. In Group 4 MRI showed signal intensity changes suggestive of cystic lesions compared to persisting echogenicity on US (n = 3) and an asymmetrical PLIC (n = 5), which predicted hemiplegia in 4. CONCLUSION: Early MRI especially provided additional information in those with c-PVL. MRI at term age could assess the PLIC, which was useful in children with unilateral parenchymal involvement, for prediction of subsequent hemiplegia and, to a lesser degree, in bilateral c-PVL for prediction of diplegia or quadriplegia.     

Imaging appearance of myelopathy secondary to nitrous oxide abuse: a case report and review of the literature

Purpose The abuse of nitrous oxide (N₂O) can induce Vitamin B₁₂ deficiency that subsequently leads to central nervous demyelination, myelopathy and peripheral neuropathy. Although myelopathy has been reported in the past, the specific locations and prognosis of the disease are still unclear.

Materials and methods: We report the case of a 22-year-old male who presented with quadriplegia that began after a 3-month history of inhalation of N₂O. We summarized the clinical data of this entity and performed a comprehensive literature review of various presentations and MRI features of myelopathy secondary to N₂O abuse.

Results: In combination with previous reports of 14 cases, we found that the onset of the disease was usually subacute, and the majority of patients (92.85%) were young men. There was no definite relationship between myelopathy and the amount or duration of N₂O inhalation. The most common clinical manifestation was sensory ataxia, and the cervical spinal cord was the most frequently impaired area of the whole spinal cord. The spinal cord lesions had a high signal intensity on T2-weighted MRI and usually involved more than three spinal segments and impaired the posterior column more significantly. Most patients recovered well after vitamin B₁₂ supplementation.

Conclusions: Myelopathy secondary to N₂O abuse is generally seen in young men. The clinical diagnosis mainly depends on a history of N₂O inhalation and the characteristic imaging changes in the posterior cervical spinal cord. Early diagnosis and intervention are important for a satisfactory prognosis.     

Influence of 100% and 40% oxygen on penumbral blood flow,oxygen level,and T2*-weighted MRI in a rat stroke model

Accurate imaging of the ischemic penumbra is a prerequisite for acute clinical stroke research. T₂^* magnetic resonance imaging (MRI) combined with an oxygen challenge (OC) is being developed to detect penumbra based on changes in blood deoxyhemoglobin. However, inducing OC with 100% O₂ induces sinus artefacts on human scans and influences cerebral blood flow (CBF), which can affect T₂^* signal. Therefore, we investigated replacing 100% O₂ OC with 40% O₂ OC (5 minutes 40% O₂ versus 100% O₂) and determined the effects on blood pressure (BP), CBF, tissue p₂, and T₂^* signal change in presumed penumbra in a rat stroke model. Probes implanted into penumbra and contralateral cortex simultaneously recorded p₂ and CBF during 40% O₂ (n=6) or 100% O₂ (n=8) OC. In a separate MRI study, T₂^* signal change to 40% O₂ (n=6) and 100% O₂ (n=5) OC was compared. Oxygen challenge (40% and 100% O₂) increased BP by 8.2% and 18.1%, penumbra CBF by 5% and 15%, and penumbra p₂ levels by 80% and 144%, respectively. T₂^* signal significantly increased by 4.56%±1.61% and 8.65%±3.66% in penumbra compared with 2.98%±1.56% and 2.79%±0.66% in contralateral cortex and 1.09%±0.82% and −0.32%±0.67% in ischemic core, respectively. For diagnostic imaging, 40% O₂ OC could provide sufficient T₂^* signal change to detect penumbra with limited influence in BP and CBF.     

(1)H-MRS profile in MRI positive- versus MRI negative patients with temporal lobe epilepsy.

INTRODUCTION: The objective of this study was to quantitate and compare ipsilateral total N-acetyl aspartate (tNAA), creatine (Cr), choline (Cho), myo-inositol (m-Ins) and glutamate plus glutamine (Glx) levels in the hippocampi of patients with temporal lobe epilepsy (TLE) with and without magnetic resonance imaging (MRI) evidence for mesial temporal sclerosis (MRI positive/negative). PATIENTS AND METHODS: Twenty-three age matched healthy controls and 26 consecutive patients with unilateral TLE, based on intensive 24h video-EEG, were investigated with proton magnetic resonance spectroscopy ((1)H-MRS) (17 with unilateral hippocampal sclerosis (HS) in MRI-MRI positive; 9 MRI negative). For statistical analysis one-way analysis of variance (ANOVA) with post hoc multiple comparisons and Bonferroni correction was applied. The significance level was based on p<0.05. RESULTS: The mean tNAA level ipsilateral to the seizure focus was significantly decreased in MRI negative, respectively MRI positive patients in comparison to healthy controls (p<0.001). The lowest tNAA level was noticed in the MRI positive group (p<0.001). Statistical analysis highlighted a clear "tNAA cut-off" (95% confidence interval) between MRI positive- and MRI negative patients and healthy controls. Mean level of Glx and m-Ins was not significantly elevated or reduced. However, in individual cases a significant elevation was noticed for Glx in MRI negative patients, respectively for m-Ins in MRI positive patients. CONCLUSION: MRI negative TLE patients have a different MRS profile than MRI positive patients (HS) with marginal but significant decrease of tNAA. Our results reveal a clear "tNAA cut-off" between the groups. The value of m-Ins and Glx in focus detection in TLE patients remains controversy.     

Changes in rat cerebral blood volume due to modulation of the 5-HT1A receptor measured with susceptibility enhanced contrast MRI

Brain blood volume changes in the rat in response to 5-HT_1A agonist and antagonist administration were measured using susceptibility contrast enhanced magnetic resonance imaging (MRI). Administration of the 5-HT_1A agonist 8-OH-DPAT resulted in decreases in fractional brain blood volumes. Administration of the 5-HT_1A antagonist WAY-100635 following a dose of 8-OH-DPAT resulted in increases in fractional blood volumes greatest in hippocampus and cortex and smallest in thalamus and caudate-putamen. The magnitude of the regional increases in blood volumes paralleled the distribution of 5-HT_1A receptors in the rat brain. Administration of WAY-100635 alone resulted in decreases in cortical blood volume and increases in cerebellar blood volume.     

Periventricular and white matter magnetic resonance imaging hyperintensities do not differ between Alzheimer's disease and normal aging

We studied normotensive and nondiabetic subjects, free of cardiac disorders, to determine whether Alzheimer's disease is a possible factor of magnetic resonance imaging (MRI) white matter or periventricular hyperintensities, and to investigate relationships between computed tomographic scan and MRI changes. We failed to reveal (1) any difference in the severity of MRI white matter and periventricular hyperintensities between patients and controls, (2) any correlation of MRI white matter and periventricular hyperintensities with either ages or Mini-Mental State Examination scores. We found (1) a poor interobserver agreement, and (2) a correlation between computed tomographic scan and MRI white matter changes but not between computed tomographic and MRI periventricular changes. We conclude that MRI periventricular and white matter hyperintensities are frequent incidental findings in the elderly and do not significantly differ between patients with Alzheimer's disease and healthy controls.     

Utility of magnetic resonance imaging in acute intracerebral hemorrhage.

The authors determine whether magnetic resonance imaging (MRI) during acute hospitalization for spontaneous intracerebral hemorrhage (ICH) provides new diagnostic information. ICD-9 codes were used to identify consecutive patients with spontaneous ICH at Hermann Hospital, Houston, Texas, between January 1995 and August, 1997. Two investigators employed rigorous criteria to determine whether the MRI findings led to a specific new diagnosis. Two hundred ninety-one patients met inclusion and exclusion criteria. Sixty-seven (23%) patients underwent brain MRI during the acute hospitalization. MRI provided a new diagnosis in 15 of these 67 patients (22%). Amyloid angiopathy and vascular malformation (four each) were the most frequently identified etiologies. The yield of MRI was low in basal ganglia and thalamic hemorrhage. Two of 23 (9%) patients with deep ICH and 13 of 44 (30%) patients with lobar and infratentorial hemorrhage had etiology determined by MRI. Timing of MRI did not affect yield.     

Utility of magnetic resonance imaging in diagnosing ulnar neuropathy at the elbow.

OBJECTIVE: Magnetic resonance imaging (MRI) of the ulnar nerve is being increasingly employed in the diagnosis of ulnar neuropathy at the elbow (UNE). Our aims were to: (i) assess the sensitivity of MRI in diagnosing UNE, especially in cases where neurophysiologic studies were non-localizing, (ii) determine the spectrum of MRI abnormalities in patients presenting with symptoms and signs of ulnar neuropathy, (iii) assess whether MRI findings differ between grades of UNE severity, and (iv) to see if MRI findings give an input into the pathological mechanisms of UNE. METHODS: Clinical, neurophysiologic, and radiologic (MRI) records were reviewed in 52 patients with symptoms and signs of ulnar neuropathy. Ulnar nerve MRI studies were assessed by an unblinded observer. RESULTS: The sensitivity of MRI at diagnosing UNE was higher than conventional nerve conduction studies, 90 versus 65%, respectively. In patients with non-localizing neurophysiologic studies (n=19), MRI disclosed changes consistent with UNE in 16 (84%) cases. The most frequent MRI findings included a combination of high signal intensity and nerve enlargement (63%), followed by nerve compression (27%) and isolated high signal intensity (23%), and isolated nerve enlargement (2%). There was no significant difference between patients with localizing and non-localizing neurophysiologic testing. Lastly, there were no differences between different grades of UNE, suggesting that UNE may be a neurophysiologically heterogeneous disorder. CONCLUSIONS: MRI studies proved to be more sensitive than conventional nerve conduction studies at diagnosing UNE. In addition, the MRI studies were highly sensitive in patients with non-localizing UNE. SIGNIFICANCE: Our study shows that MRI of the ulnar nerve should be used in patients with clinical features of UNE especially in those with non-localizing neurophysiologic testing.     

Will MRI replace the EEG for the diagnosis of nonconvulsive status epilepticus,especially focal?

Magnetic resonance imaging (MRI) can now be used to diagnose or to provide confirmation of focal nonconvulsive status epilepticus (NCSE). Approximately half of patients with status epilepticus (SE) have signal changes. MRI can also aid in the differential diagnosis with generalized NCSE when there is a clinical or EEG doubt, e.g. with metabolic/toxic encephalopathies or Creutzfeldt-Jakob disease. With the development of stroke centers, MRI is available 24 h/24 in most hospitals. MRI has a higher spatial resolution than electroencephalography (EEG). MRI with hyperintense lesions on FLAIR and DWI provides information related to brain activity over a longer period of time than a standard EEG where only controversial patterns like lateralized periodic discharges (LPDs) may be recorded. MRI may help identify the ictal nature of LPDs. The interpretation of EEG tracings is not easy, with numerous pitfalls and artifacts. Continuous video-EEGs require a specialized neurophysiology unit. The learning curve for MRI is better than for EEG. It is now easy to transfer MRI to a platform with expertise. MRI is more accessible than single photon emission computed tomography (SPECT) or positron emission tomography (PET). For the future, it is more interesting to develop a strategy with MRI than SPECT or PET for the diagnosis of NCSE. With the development of artificial intelligence, MRI has the potential to transform the diagnosis of SE. Additional MRI criteria beyond the classical clinical/EEG criteria of NCSE (rhythmic versus periodic, spatiotemporal evolution of the pattern…) should now be systematically added. However, it is more complicated to move patients to MRI than to perform an EEG in the intensive care unit, and at this time, we do not know how long the signal changes persist after the end of the SE. Studies with MRI at fixed intervals and after SE cessation are necessary.     

MRI-clinical correlations in the primary progressive course of MS: new insights into the disease pathophysiology from the application of magnetization transfer,diffusion tensor,and functional MRI

Despite patients with primary progressive multiple sclerosis (PPMS) experience a progressive disease course from onset, the burden and activity of lesions on conventional magnetic resonance imaging (MRI) scans of the brain are lower than in all other main clinical phenotypes of MS. This review outlines the major contributions given by magnetization transfer MRI, diffusion tensor MRI and functional MRI to the understanding of the pathophysiology of PPMS and provides evidence that, at least, three factors might explain this clinical/MRI discrepancy: (a) the presence of a diffuse tissue damage at a microscopic level; (b) a prevalent involvement of the cervical cord, and (c) an impairment of the adaptive capacity of the cortex to limit the functional consequences of subcortical structural damage.