Conventional Magnetic Resonance Imaging Techniques Research Articles

Quantitative Brain MRI

This issue of Topics in Magnetic Resonance Imaging (MRI) is about “Quantitative Brain MRI.” What do we mean by “quantitative” MRI? In the context of imaging studies, the term quantitative is often used when numeric values of signal intensities are measured in addition to performing the conventional “qualitative” visual inspection of the images. For example, a region of interest analysis or tissue segmentation and classification based on relative signal intensities are often referred to as “quantitative.” Here, we consider a more stringent definition of the term quantitative. We regard an MRI study to be quantitative when we obtain maps of meaningful physical or chemical variables that can be measured in physical units and compared between tissue regions and among subjects. By this definition, most clinical MRI acquisitions are not quantitative. Traditionally, clinical MRI relies on the acquisition of so-called weighted images, whose image contrast is affected by a combination of different factors, some intrinsic to the tissue and some dependent on the specifics of the experiment. The diagnostic utility of conventional MRI in many neurological disorders is unquestionable; however, the domain of conventional MRI is limited to revealing either gross morphological abnormalities or focal abnormalities resulting in regional differences in signal intensities within a given brain. To detect pathology, conventional MRI relies on differences in contrast between areas that are “supposedly” affected and areas that are “supposedly” normal. Conventional MRI is intrinsically insensitive to subtle global changes that may affect the entire brain. There is no doubt that a more widespread use of quantitative MRI methods is desirable. They will increase the sensitivity of clinical brain MRI by allowing the comparison of measurements in a single subject with normative values acquired in a healthy population and will provide the foundations for monitoring subtle changes caused by the progression or remission of disease. Another limitation of conventional MRI techniques is their lack of biological specificity; that is, different physiological and pathological substrates can produce similar changes in image contrast. For example, hyperintensity in T2-weighted images can originate from a number of factors such as edema, demyelination, dysmyelination, axonal loss, and necrosis. Although quantification per se does not ensure biological specificity, it represents an important component of any metric that is an imaging “biomarker” candidate. Given that the advantages of more quantitative approaches in neuroimaging seem obvious, why does clinical neuroradiology still rely almost completely on qualitative techniques? In this edition of Topics in Magnetic Resonance Imaging, we asked experts of several MRI techniques used in neuroimaging studies to discuss quantification issues in their respective fields by providing a balanced report not only on recent progress and future promises but also on standing obstacles. All authors are well known for having provided fundamental theoretical and scientific contributions and also for working extensively on the dissemination and clinical implementation of their respective techniques. They cover (1) perfusion MRI using arterial spin labeling (Jiongjiong Wang et al), (2) perfusion MRI using dynamic-susceptibility contrast (Fernando Calamante), (3) diffusion MRI (Derek Jones), (4) MRI proton relaxometry (Sean Deoni), and (5) proton magnetic resonance spectroscopy and spectroscopic imaging (Jeffry Alger). In addition to these technique-specific contributions, in the closing paper of this issue, Ona Wu et al discuss the use of multiparametric MRI techniques for the characterization and clinical investigation of brain disorders. Although, given time constraints, multiparametric assessment is usually done using “qualitative” signal measurements, the ability to perform a meaningful analysis of multiparametric data is an important and promising aspect of quantitative MRI. We hope that this issue will provide clinical researchers with information helpful to evaluate the feasibility of using quantitative neuroimaging approaches in their work. It seems that, with recent technological improvements, several neurological conditions could be investigated using quantitative MRI techniques if carefully designed time-efficient scanning protocols are developed.

Structural and functional neuroimaging in intractable epilepsy

Medical management remains unsatisfactory in about a third of patients with epilepsy and some of them are candidates for resective epilepsy surgery. Structural and functional neuroimaging plays an important role in the identification of the precise cortical region responsible for seizures and is very crucial for a good surgical outcome. Furthermore, identification of eloquent cortical areas near the region to be resected is essential to avoid postoperative neurologic deficit. The magnetic resonance imaging (MRI) protocol for epilepsy can be individually tailored depending on the seizure semiology and possibly electroencephalography. New MRI techniques demonstrate the structure of the brain in fine detail, help in understanding the underlying pathology, and demonstrate functional activity of the brain with high spatial and temporal resolution. Metabolic imaging techniques, such as positron emission tomography (PET) and single photon emission tomography (SPECT) visualize metabolic alterations of the brain in the ictal and interictal states. In MR-negative epilepsy patients, these techniques may have localizing value. The proper use and interpretation of the findings provided by these new technologies is crucial. In this review article, we discuss various conventional and advanced MRI techniques, interpretation of various findings, and the role of functional imaging modalities, such as functional MRI, PET, and SPECT in the localization of epileptogenic substrate as well as for understanding the pathophysiology, propagation, and neurochemical correlates of epilepsy.

Advances in neuroimaging of traumatic brain injury and posttraumatic stress disorder.

Improved diagnosis and treatment of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are needed for our military and veterans, their families, and society at large. Advances in brain imaging offer important biomarkers of structural, functional, and metabolic information concerning the brain. This article reviews the application of various imaging techniques to the clinical problems of TBI and PTSD. For TBI, we focus on findings and advances in neuroimaging that hold promise for better detection, characterization, and monitoring of objective brain changes in symptomatic patients with combat-related, closed-head brain injuries not readily apparent by standard computed tomography or conventional magnetic resonance imaging techniques.

Parkinsonian syndromes

The primary role of magnetic resonance imaging (MRI) in the evaluation of patients with parkinsonian syndromes is traditionally thought to be the differentiation between neurodegenerative and symptomatic parkinsonisms. Non conventional MRI techniques, however, could improve the clinical diagnosis by detecting ultrastructural damage even in brain regions not suspected to be involved. Moreover, functional MRI provides useful information upon the pathophysiology of Parkinson's disease.

Neuromelanin-Sensitive MRI

The basics and the technique of magnetic resonance imaging (MRI) for visualizing the neuromelanin present in dopaminergic and noradrenergic nuclei in the substantia nigra pars compacta (SNc) and locus caeruleus (LC) are introduced. Neuromelanin, a black pigment produced during catecholamine synthesis, has paramagnetic T1-shortening effects. Conventional MRI techniques fail to depict the contrast generated by neuromelanin, but neuromelanin-sensitive T1-weighted fast spin echo technique at 3 T allows the direct visualization of the SNc and LC as hyperintense areas. In Parkinson's disease, neuromelanin-related signals from the SNc and LC are diminished, suggesting neuronal degeneration in both the nuclei. In depression and schizophrenia, signals from the LC are reduced while those from the SNc are augmented, suggesting monoamine and dopamine hypotheses, respectively. Neuromelanin-sensitive MRI is a promising technique to elucidate the pathologic or functional changes in the catecholamine neurons of the brain stem that occur in degenerative and psychiatric diseases.

Advances in Magnetic Resonance Imaging of the Injured Neonatal Brain

<P>In spite of improvement in neonatal medicine, neonatal encephalopathy and resulting neonatal brain injury is a major complication that can cause long-term disability. Multiple neuroscience studies have determined potential mechanisms that underlie the vulnerability of the neonatal brain to multiple insults. In the near future, there may be new therapeutic options for both prevention and treatment of neonatal brain injury. Most pediatric centers currently use cranial ultrasound to evaluate neonatal brain injury. In the past decade, magnetic resonance imaging (MRI) techniques have been shown to be a useful additive imaging tool in the evaluation of neonatal brain injury. Conventional MRI techniques have been shown not only to provide valuable information about the pattern of brain injury in the neonatal period but also to provide information about prognosis and neurodevelopment outcome. There have been recent advances in MRI of neonatal encephalopathy with respect to the development of MR-compatible incubators. These incubators can provide an environment specifically adapted to meet the needs of critically ill preterm and term neonates when undergoing MRI. In addition, imaging resolution and signal-to-noise ratio (SNR) have been improved dramatically with the use of specifically designed neonatal coils. MR diffusion (both diffusion-weighted imaging and diffusion-tensor imaging) and MR spectroscopy are recently developed techniques that are now used routinely. The goals of this article are to provide information about the technological MR advances in the evaluation of the injured neonatal brain and to review clinical examples, which are in the major differential diagnoses of neonatal brain injury including perinatal white matter injury, hypoxic-ischemic brain injury, metabolic disease, and hemorrhage.</P> <H4>ABOUT THE AUTHORS</H4> <P>Ashok Panigrahy, MD; and Stefan Blüml, PhD, are with the Department of Radiology, Division of Neuroradiology, Institute for Maternal Fetal Health, Childrens Hospital Los Angeles (CHLA), Keck School of Medicine of USC, Los Angeles, California.</P> <P>Address correspondence to: Ashok Panigrahy, MD, Childrens Hospital Los Angeles, Department of Radiology, Mail Stop #81, 4650 Sunset Blvd., Los Angeles, CA 90027; or e-mail <a href="mailto:apanigrahy@chla.usc.edu">apanigrahy@chla.usc.edu</a>.</P> <P>Dr. Panigrahy and Dr. Bluml have disclosed no relevant financial relationships.</P> <P>The authors thank Marvin D. Nelson, MD; Istvan Seri, MD; Floyd Gilles, MD; and the Neonatal Intensive Care Unit (NICU) and Magnetic Resonance Imaging (MRI) staff at CHLA for support and advice. The authors thank Julia Cruz and Madalyn Shrier for editorial support. Grant support is from the Radiological Society of North America (RSNA), Rudi Schulte Research Institute, and National Institutes of Health (NIH) pediatric research loan repayment grant.</P> <H4>EDUCATIONAL OBJECTIVES</H4> <OL> <LI>Identify recent technological advances in the evaluation of the injured neonatal brain using magnetic resonance imaging (MRI).</LI> <LI>Propose clinical examples of neonatal brain injury as they are delineated via MRI.</LI> <LI>Differentiate the advantages of MRI evaluation of neonatal brain injury over the current standard of ultrasound imaging.</LI> </OL>

10B-editing 1H-detection and 19F MRI strategies to optimize boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a binary radiation therapy used to treat malignant brain tumours. It is based on the nuclear reaction (10B + n th --> [11B*] --> alpha + 7Li + 2.79 MeV) that occurs when 10B captures a thermal neutron to yield alpha particles and recoiling 7Li nuclei, both responsible of tumour cells destruction by short range and high ionization energy release. The clinical success of the therapy depends on the selective accumulation of the 10B carriers in the tumour and on the high thermal neutron capture cross-section of 10B. Magnetic resonance imaging (MRI) methods provide the possibility of monitoring, through 10B nuclei, the metabolic and physiological processes suitable to optimize the BNCT procedure. In this study, spatial distribution mapping of borocaptate (BSH) and 4-borono-phenylalanine (BPA), the two boron carriers used in clinical trials, has been obtained. The BSH map in excised rat brain and the 19F-BPA image in vivo rat brain, representative of BPA spatial distribution, were reported. The BSH image was obtained by means of double-resonance 10B-editing 1H-detection sequence, named M-Bend, exploiting the J-coupling interaction between 10B and 1H nuclei. Conversely, the BPA map was obtained by 19F-BPA using 19F-MRI. Both images were obtained at 7 T, in C6 glioma-bearing rat brain. Our results demonstrate the powerful of non conventional MRI techniques to optimize the BNCT procedure.

MR in the diagnosis and monitoring of multiple sclerosis: An overview

Multiple sclerosis is a chronic, persistent inflammatory–demyelinating disease of the central nervous system that typically presents as an acute clinically isolated syndrome attributable to a monofocal or multifocal demyelinating lesion, which usually affects the optic nerve, spinal cord, or brainstem and cerebellum. Although the diagnosis of multiple sclerosis is still based on clinical findings, magnetic resonance imaging is now integrated in the overall diagnostic scheme of the disease because of its unique sensitivity to demonstrate the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Conventional magnetic resonance imaging techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences are highly sensitive in detecting multiple sclerosis plaques and provide a quantitative assessment of inflammatory activity and lesion load. However, there is a persisting mismatch between clinical and magnetic resonance imaging efficacy of approved treatments, which underlies the fact that this technique does not suffice to explain the entire spectrum of the disease process. In recent years, great effort has been dedicated to overcoming these limitations by using non-conventional magnetic resonance-derived metrics that can selectively measure the more destructive aspects of multiple sclerosis pathology and monitor the reparative mechanisms. These metrics, which include unenhanced T1-weighted imaging, measures of central nervous system atrophy, magnetization transfer imaging, proton magnetic resonance spectroscopy, diffusion-weighted imaging, and functional magnetic resonance imaging, provide a better approximation of the pathological substrate of the multiple sclerosis plaques, have increased our understanding of the pathogenesis of the disease, and have proven useful for studying the natural history of multiple sclerosis and monitoring the effects of new treatments. Therefore, magnetic resonance imaging not only plays an essential role in the diagnosis of multiple sclerosis, but can also serve as a true biological marker of the severity of this disease.

MRI in Multiple Sclerosis: What’s Inside the Toolbox?

Magnetic resonance imaging (MRI) has played a central role in the diagnosis and management of multiple sclerosis (MS). In addition, MRI metrics have become key supportive outcome measures to explore drug efficacy in clinical trials. Conventional MRI measures have contributed to the understanding of MS pathophysiology at the macroscopic level yet have failed to provide a complete picture of underlying MS pathology. They also show relatively weak relationships to clinical status such as predictive strength for clinical progression. Advanced quantitative MRI measures such as magnetization transfer, spectroscopy, diffusion imaging, and relaxometry techniques are somewhat more specific and sensitive for underlying pathology. These measures are particularly useful in revealing diffuse damage in cerebral white and gray matter and therefore may help resolve the dissociation between clinical and conventional MRI findings. In this article, we provide an overview of the array of tools available with brain and spinal cord MRI technology as it is applied to MS. We review the most recent data regarding the role of conventional and advanced MRI techniques in the assessment of MS. We focus on the most relevant pathologic and clinical correlation studies relevant to these measures.

Recent Neuroimaging Techniques in Mild Traumatic Brain Injury

Recent Neuroimaging Techniques in Mild Traumatic Brain Injury

Noninvasive Measurement and Quantitation of Brain Iron in Parkinson’s Disease Using Adiabatic T2ρ and T1ρ High Field MRI Techniques

Postmortem demonstration of increased iron in the substantia nigra (SN) is a well- appreciated finding in Parkinson’s disease (PD). It is thought that this iron may facilitate the generation of free radicals which are thought to play a role in dopamine neuronal loss. To date, however, researchers have been unable to confirm an in vivo difference of iron between those with PD and control subjects using magnetic resonance imaging (MRI). This may be due to the limitations of T1 and T2: two conventional MRI techniques that have been employed. Here, novel T2ρ and T1ρ MRI relaxation methods were used for the measurement of iron load and distribution [1] , [2] , [3] . T2ρ measurements are indicative of tissue iron content and distribution and measure molecular motion in local susceptibility gradients. T1ρ measurements, on the other hand, can be used to assess cellular loss. When applied at high magnetic fields these two methods may provide a noninvasive and reliable handle on iron accumulation and neuronal loss in PD. In our 4 Tesla magnet study, we found a significant change of the T1ρ and T2ρ relaxation time constants (both the distribution and absolute values) in the PD group versus controls. Relaxogram analysis of the T2ρ and T1ρ measurements demonstrated increased water and iron content, as well as changes in iron distribution in the SN. Therefore, high resolution MRI with T2ρ and T1ρ provide unique information in Parkinson’s disease patients as compared to conventional T1 and T2 measurements. This information may prove useful in evaluating the pathogenesis and severity of PD. Future studies are underway to correlate T1ρ, T2ρ, and Τ2 findings with simultaneous spectroscopy measurements of absolute concentration of NAA [4] to further assess iron accumulation and neuronal loss in controls and those with PD.

Designing long‐T2 suppression pulses for ultrashort echo time imaging

Ultrashort echo time (UTE) imaging has shown promise as a technique for imaging tissues with T2 values of a few milliseconds or less. These tissues, such as tendons, menisci, and cortical bone, are normally invisible in conventional magnetic resonance imaging techniques but have signal in UTE imaging. They are difficult to visualize because they are often obscured by tissues with longer T2 values. In this article, new long-T2 suppression RF pulses that improve the contrast of short-T2 species are introduced. These pulses are improvements over previous long-T2 suppression pulses that suffered from poor off-resonance characteristics or T1 sensitivity. Short-T2 tissue contrast can also be improved by suppressing fat in some applications. Dual-band long-T2 suppression pulses that additionally suppress fat are also introduced. Simulations, along with phantom and in vivo experiments using 2D and 3D UTE imaging, demonstrate the feasibility, improved contrast, and improved sensitivity of these new long-T2 suppression pulses. The resulting images show predominantly short-T2 species, while most long-T2 species are suppressed.

Assessment of Human Disc Degeneration and Proteoglycan Content Using T1ρ-weighted Magnetic Resonance Imaging

T1rho relaxation was quantified and correlated with intervertebral disc degeneration and proteoglycan content in cadaveric human lumbar spine tissue. To show the use of T1rho-weighted magnetic resonance imaging (MRI) for the assessment of degeneration and proteoglycan content in the human intervertebral disc. Loss of proteoglycan in the nucleus pulposus occurs during early degeneration. Conventional MRI techniques cannot detect these early changes in the extracellular matrix content of the disc. T1rho MRI is sensitive to changes in proteoglycan content of articular cartilage and may, therefore, be sensitive to proteoglycan content in the intervertebral disc. Intact human cadaveric lumbar spines were imaged on a clinical MR scanner. Average T1rho in the nucleus pulposus was calculated from quantitative T1rho maps. After MRI, the spines were dissected, and proteoglycan content of the nucleus pulposus was measured. Finally, the stage of degeneration was graded using conventional T2 images. T1rho decreased linearly with increasing degeneration (r = -0.76, P < 0.01) and age (r = -0.76, P < 0.01). Biochemical analysis revealed a strong linear correlation between T1rho and sulfated-glycosaminoglycan content. T1rho was moderately correlated with water content. Results from this study suggest that T1rho may provide a tool for the diagnosis of early degenerative changes in the disc. T1rho-weighted MRI is a noninvasive technique that may provide higher dynamic range than T2 and does not require a high static field or exogenous contrast agents.

Acute Ischemic Stroke: Accuracy of Diffusion-weighted MR Imaging—Effects ofbValue and Cerebrospinal Fluid Suppression

To prospectively determine which diffusion-weighted magnetic resonance (MR) imaging technique (ie, conventional diffusion-weighted MR imaging [b = 1000 or 1500 sec/mm2] or fluid-inversion prepared diffusion [FLIPD] MR imaging [b = 1500 sec/mm2]) is most accurate in depicting acute ischemic stroke at 3 T. The Health Research Ethics Board approved this study; written informed consent was provided by all participants or their surrogate. Diffusion-weighted MR imaging was performed in 75 consecutive patients (43 men, 32 women; mean age, 64.0 years) with acute ischemic stroke. Two experienced neuroradiologists determined the presence of hyperacute stroke lesions at diffusion-weighted MR imaging by locating areas of hyperintensity that corresponded to regions with a decreased diffusion coefficient. These findings were used as the reference standard. Four raters who were blinded to patient history assessed all images and apparent diffusion coefficient maps for the presence of changes that were consistent with acute ischemic stroke. Accuracy, sensitivity, specificity, negative predictive value, positive predictive value, and inter- and intrarater reliability scores were calculated for each technique. Specificity, positive predictive value, and accuracy were not significantly different among the techniques. FLIPD MR images obtained with a b value of 1500 sec/mm2 had decreased sensitivity for acute ischemic stroke (mean, 61.8%; 95% confidence interval [CI]: 55.4%, 67.9%) compared with conventional diffusion-weighted MR images obtained with a b value of either 1000 sec/mm2 (mean, 82.5%; 95% CI: 77.1%, 87.0%) or 1500 sec/mm2 (mean, 84.5%; 95% CI: 79.3%, 88.9%). FLIPD MR images also had decreased negative predictive value (mean, 96.5%; 95% CI: 95.7%, 97.2%) compared with conventional diffusion-weighted MR images obtained with a b value of either 1000 sec/mm2 (mean, 98.4%; 95% CI: 97.8%, 98.8%) or 1500 sec/mm2 (mean, 98.6%; 95% CI: 98.1%, 99.0%). Intra- and interrater reliability scores were generally excellent for all three techniques. FLIPD MR images obtained with a b value of 1500 sec/mm2 are less suitable for the detection of acute ischemic stroke owing to a decreased sensitivity and negative predictive value. The performance of the two conventional diffusion-weighted MR imaging techniques (b = 1000 and 1500 sec/mm2) was equivalent.

Magnetic Resonance Imaging Monitoring of Multiple Sclerosis Lesion Evolution

The characteristic feature of multiple sclerosis (MS) pathology is the demyelinated plaque distributed throughout the central nervous system. Although MS is a primary demyelinating disease, acute axonal injury is common in actively demyelinating MS lesions and it is considered one of the major determinants of neurological deficit. Magnetic resonance imaging (MRI) has had a dramatic impact on MS in both the clinical practice and basic science settings. Techniques such as T2-weighted and gadolinium-enhanced T1-weighted MRI are very sensitive in detecting lesions and, thus, increase the level of certainty of MS diagnosis. Conventional MRI has also improved our understanding of the pathogenesis of the disease and has provided objective and reliable measures to monitor the effect of experimental treatments in clinical trials. However, conventional MRI does not provide specific information on the heterogeneous pathologic substrate of MS lesions. Advanced MRI techniques, such as magnetization transfer imaging, diffusion tensor imaging, and proton MR spectroscopy, offer the unprecedented ability to observe and quantify pathological changes in lesions and normal-appearing brain tissue over time. The present review will discuss the major contributions of conventional MRI and quantitative MRI techniques to understand how individual MS lesions evolve.

Magnetic Resonance Imaging Advances in Multiple Sclerosis

Magnetic resonance imaging (MRI) has become a core component of clinical management and scientific research in multiple sclerosis (MS), providing essential information about tissue structure and function. MRI is now the most important laboratory diagnostic and longitudinal monitoring technology. A number of conventional MRI techniques, which include T2-weighted, T1-weighted, and gadolinium-enhanced imaging, are used to identify overt lesions and quantify tissue atrophy. MRI is highly sensitive in detecting brain and spinal cord involvement in MS and can visualize multifocal lesions, occult disease, and macroscopic atrophy. Advanced MRI techniques, such as magnetization transfer imaging, spectroscopy, diffusion-weighted imaging, and functional MRI, have added to our understanding of the pathogenesis of the disease. The precise role of these newer imaging approaches continues to be defined. In this supplement to the Journal of Neuroimaging, the authors review the role of conventional and advanced MRI techniques in detecting tissue changes in MS, diagnosing and monitoring patients, and charting the progression of disease in new and established patients.

An update on conventional and advanced magnetic resonance imaging techniques in the differential diagnosis of neurodegenerative parkinsonism

The clinical differentiation between Parkinson's disease and atypical parkinsonian disorders (APD) remains a challenge for every neurologist. Conventional magnetic resonance imaging (MRI) and different advanced MRI techniques offer the potential for objective criteria in the differential diagnosis of neurodegenerative parkinsonism. The aim of this article is to review the recent literature on the role of conventional and advanced MRI techniques in the differential diagnosis of neurodegenerative parkinsonian disorders. An important role of MRI is the exclusion of symptomatic parkinsonism due to other pathologies. Over the past two decades, conventional MRI and different advanced MRI techniques, including proton magnetic resonance spectroscopy (1H-MRS), diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and magnetic resonance volumetry (MRV) have been found to show abnormalities in the substantia nigra and basal ganglia, especially in APD. Recent studies using MRV, MTI, DWI and 1H-MRS to discriminate Parkinson's disease from APD are discussed extensively. Research findings suggest that novel MRI techniques such as MTI, DWI and MRV have superior sensitivity compared to conventional MRI in detecting abnormal features in neurodegenerative parkinsonian disorders. Whether these techniques will emerge as standard investigations in the work-up of patients presenting with parkinsonism requires further prospective magnetic resonance studies during early disease stages.

Imaging of Multiple Sclerosis: Role in Neurotherapeutics

Magnetic resonance imaging (MRI) plays an ever-expanding role in the evaluation of multiple sclerosis (MS). This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected clinically isolated syndromes. In addition, MRI is a key tool in providing primary therapeutic outcome measures for phase I/II trials and secondary outcome measures in phase III trials. The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called normal-appearing brain tissue). However, all current MRI methodology suffers from limited specificity for the underlying histopathology. Conventional MRI techniques, including lesion detection and measurement of atrophy from T1- or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials, in which the use of gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation. Advanced imaging methods including magnetization transfer, fluid attenuated inversion recovery, diffusion, magnetic resonance spectroscopy, functional MRI, and nuclear imaging techniques have added to our understanding of the pathogenesis of MS and may provide methods to monitor therapies more sensitively in the future. However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on neurotherapeutics.

Color-coded diffusion-tensor-imaging of posterior cingulate fiber tracts in mild cognitive impairment

Different processes like microvascular dysfunction, free radical toxicity, β-amyloid deposits, and Wallerian degeneration can cause functionally relevant disturbances of cerebral neuronal networks by myelin degeneration. Color-coded diffusion-tensor-imaging (ccDTI) allows the structural identification and quantification of myelinated fiber tracts. Particularly, posterior cingulate fiber tracts, which are regarded as important neuronal substrates of the network representing memory processing can be localized only imprecisely by conventional magnetic resonance imaging techniques. The posterior cingulate bundles were assessed by ccDTI in 17 patients with amnestic mild cognitive impairment (MCI), 25 patients with Alzheimer's dementia (DAT), and 21 age-matched controls. Additionally, DTI values were correlated with memory performance in the delayed verbal recall test. Fractional anisotropy and mean diffusivity differed significantly between MCI and controls, as well as between DAT and controls. Performance in the delayed verbal recall test of the entire study group correlated significantly with posterior cingulate bundle anisotropy and diffusivity. Using ccDTI seems, hence, a favorable strategy to detect and quantify the structural integrity of posterior cingulate white matter in MCI. Alterations of DTI parameters substantiate the involvement of white matter pathology in the development of MCI. Moreover, ccDTI could serve as in vivo method to investigate age and disease-related myelin alterations as potential morphological substrates of cognitive dysfunction.

The use of magnetic resonance imaging in the diagnosis and long-term management of multiple sclerosis

Magnetic resonance imaging (MRI) continues to evolve, providing almost boundless information about tissue structure and function that can be obtained noninvasively in vivo. MRI is a key tool in the diagnosis and longitudinal monitoring of patients with multiple sclerosis (MS). The technique is highly sensitive for the definition of brain and spinal cord involvement in MS, including the ability to detect multifocal lesions, diffuse (occult) disease, and macroscopic atrophy. Conventional MRI techniques, which include T2-weighted, T1-weighted, and gadolinium-enhanced imaging, are used primarily to detect overt lesions but can also be used to quantify tissue atrophy. Variations of these techniques also are important, and refinements are under way. The ability to demonstrate lesion dissemination in space and time has led to the common use of MRI as a paraclinical measure to support a diagnosis of MS, including in patients with clinically isolated demyelinating syndromes. In addition, MRI is used to monitor the progress of disease in patients with clinically definite MS, including assessment of lesions and atrophy. The use of conventional MRI in the diagnosis and longitudinal management of patients with MS is the focus of this review.