Diffusion Weighted MR Imaging of the Brain

With 661 Figures and 11 Tables

Springer

ISBN-10 3-540-25359-9

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Foreword

Few advances in MR imaging have had the impact that diffusion-weighted imaging (DWI) has had in the evaluation of brain. From the time of the early descriptions by LeBihan and colleagues of the ability to image and measure the micromovement of water molecules in the brain to the present time, diffusion imaging and its derivatives have made an impact in the evaluation of multiple disease processes,primari-ly in ischemia, but also in other conditions of the brain. In most medical centers diffusion imaging is no longer considered a sequence to be used in special circumstances but rather it is employed as part of routine MR imaging of the brain. Because the information derived from diffusion measurements can improve our understanding of pathologic processes and can influence patient care, knowledge of the principles and applications of DWI is critical.

It is therefore of great interest that the group from the University of Rochester (Drs. Moritani, Ekholm, and Westesson) have assembled under one cover a collection of material which covers all the clinical aspects of diffusion-weighted imaging. Those who have attended recent meetings of the ASNR know the quality of the exhibits and presentations which have come from this group. They, early on, demonstrated the wide spectra of diseases which can cause restricted diffusion and they warned us of mimickers of infarction and ischemia.

In this richly illustrated volume the authors take the reader from the basic principles of DWI, through the pulse sequences used, to mathematical concepts behind the derivation of apparent diffusion coefficients. Following explanations of the different types of edema which can effect the brain and the appearance of DW images, this book allows the reader to see the variety of conditions which alter diffusion, including infarction, hemorrhage, cerebral infections, degenerative neurologic disorders, white matter dis eases, toxic/metabolic disorders, and tumors. As one can easily see from the table of contents, the authors have systematically covered all major areas of neuroradiology. This will allow cross-referencing to problematic cases which one may encounter. Additionally, knowledge of what represents a normal brain in adults and in the developing brain along with an explanation of artifacts seen in DWI makes this a valuable book. It is noteworthy that the authors have chosen to abundantly illustrate the clinical material, drawing on pathologic correlations in a number of areas.

I believe that this book will benefit not only those who deal routinely with neuro-MR imaging, but also those who want to establish a basis for understanding of diffusion images in the hope of taking these principles of diffusion further into more exotic areas of neuroimaging such as white matter tract mapping with diffusion tensor imaging, analyzing alterations in highly organized structures with fractional aniso-tropy, or delving into macromolecular alterations with ever-higher b values. The authors are to be congratulated for putting their considerable experience together in this form, and I am sure that the collection of cases herein will serve to educate not only those who are just entering the clinical neuro-sciences,but also those who daily use diffusion imaging to arrive at a proper clinical diagnosis.

Chairman, Department of Radiology

The Robert Shapiro, M.D. Professor of Radiology

University of Miami/Jackson Memorial

Medical Center

Miami, Florida, USA

Editor-in-Chief

American Journal of Neuroradiology

Preface

This book is the result of many years of clinical and academic interest in diffusion-weighted MR (DW) imaging of the brain. Researchers and clinicians at the University of Rochester started to collect DW images of a spectrum of abnormalities affecting the brain immediately after this technique became available. Several case series with clinical and radiographic correlations have been presented at the annual meetings of the American Society of Neuroradiology and the Radiological Society of North America via posters and scientific reports. Over time it became quite clear that we had a collection of DW images representing the majority of conditions that affect the brain and we felt a need to put them all together under one cover.

MR imaging has evolved dramatically since its introduction into clinical work in the mid-1980s. Looking back, there are several major steps that took MR imaging of the central nervous system to the next level. One of the first steps was the introduction of the clinical usefulness of contrast agents. Other steps were the development of fat suppression techniques, fast spin echo imaging, and, more recently, the development of a clinically useful DW imaging technique. DW imaging has revolutionized the imaging diagnosis of acute infarction in the brain. It is, however, quite clear from the series of cases shown in this book that DW imaging is useful for many other conditions. The time it takes to obtain a DW image is so short that in many institutions it is now being used as a routine part of any MR imaging of the brain.

The initial chapters on principles of DW imaging, normal DW appearance, and pitfalls and artifacts provide the bases for understanding DW imaging. This technique is complex and is associated with many pitfalls and artifacts. The following chapter on brain edema provides the basis for understanding the pathophysiology of signal alterations in DW images related to various pathological conditions. The images are correlated to corresponding neuropatholog-ic slides and aid the understanding of the DW imaging representation of various types of brain edema.

Chapters 5-13 cover DW imaging characteristics of different pathologic conditions and in Chap. 14 (pediatrics) we have collected DW images of pediatric conditions.

The book is organized according to major disease categories. This brings structure to the book, but is not optimal for the clinician sitting in front of a set of images and wondering what they might represent. For that reason we have a summary chapter entitled "How to Use This Book" (Chap. 15), which is organized from the opposite perspective. Thus, in Chap. 15 we have started with DW images and grouped them according to imaging characteristics. In each table we have listed differential diagnoses for each specific set of DW imaging characteristics and added thumbnail images with references to the corresponding chapters. The clinician can go directly to Chap. 15, determine the signal on the DW imaging, combine it with the T2 and ADC signal characteristics, and get a list of the conditions that match these imaging characteristics. The thumbnail images, the reference to corresponding chapter and knowledge about the patient's clinical presentation should allow the clinician to formulate a relatively narrow differential diagnosis for most clinical conditions. We think that this "reversed" chapter will make the book very useful for everyday work with DW imaging of the brain.

We are grateful for many pathological slides and fruitful discussions with Barbara Germin, MD, Department of Pathology, University of Rochester. We acknowledge the case contribution from the Department of Radiology, Showa University, Japan, collected during the primary author's time at Showa University. We would also like to thank Masahiro Ida, MD, Department of Radiology, Ebara Municipal Hospital, Japan; Minoru Morikawa, MD, Department of Radiology, Nagasaki University, Japan; R. Nuri Sener, MD, Department of Radiology, Ege University Hospital, Turkey; and Ryutarou Ukisu, MD, Department of Radiology, Showa University, Japan, all of whom contributed case studies. Our deepest gratitude goes to Ms Margaret Kowaluk and Ms Theresa Kubera, Med-

ical Graphic Designers, Department of Radiology, University of Rochester, and Ms Belinda De Libero for her secretary work. We also wish to thank Yuji Nu-maguchi, MD, PhD, Department of Radiology, University of Rochester and St. Luke's Hospital, Japan, who gave us encouragement and support.

We want to thank the editorial staff at SpringerVerlag, without whose guidance, skills and knowledgeable advice this book would not have become a reality. We would also like to thank our colleagues, fellows and coworkers at the University of Rochester. Finally, but not least, we thank our families for giving us the time to complete this project.

It is our hope that our readers will find this book on "Diffusion-Weighted Imaging of the Brain" instructional and clinically useful.

October 2003

Toshio Moritani Sven Ekholm Per-Lennart Westesson

Authors

Toshio Moritani, MD, PhD Assistant Research Professor Division of Diagnostic and Interventional Neuroradiology Department of Radiology University of Rochester School of Medicine and Dentistry Rochester, New York, USA

Akio Hiwatashi, MD

Assistant Research Professor

Division of Diagnostic and Interventional Neuroradiology

Department of Radiology

University of Rochester

School of Medicine and Dentistry

Rochester, New York, USA

Sven Ekholm, MD, PhD

Professor of Radiology and Director of Research

Division of Diagnostic and Interventional Neuroradiology

Department of Radiology

University of Rochester

School of Medicine and Dentistry

Rochester, New York

Professor of Radiology University of Gothenburg Gothenburg, Sweden

Per-Lennart Westesson, MD, PhD, DDS Professor of Radiology and Director of Division of Diagnostic and Interventional Neuroradiology Department of Radiology and Professor of Clinical Dentistry University of Rochester School of Medicine and Dentistry Rochester, New York, USA

Professor of Oral Diagnostic Sciences State University of New York at Buffalo Buffalo, New York, USA

Associate Professor of Oral Radiology University of Lund Lund, Sweden

Ramon R. de Guzman, MD

Fellow, Division of Diagnostic and Interventional Neuroradiology Department of Radiology University of Rochester Medical Center Rochester, New York, USA

Fellow, Philippine College of Radiology Philippines

Jianhui Zhong, PhD

Associate Professor of Radiology, Biomedical Engineering, and Physics Director of MR Imaging Research Department of Radiology University of Rochester School of Medicine and Dentistry Rochester, New York, USA

Associate Professor of Radiology Yale University School of Medicine New Haven, Connecticut, USA

Contents

1 Basics of Diffusion Measurements by MRI 1

1.1 Diffusion Imaging in MR 1

1.2 Diffusion Imaging of the Brain 1

1.3 Magnetic Resonance Principles of Diffusion Imaging 1

1.4 Apparent Diffusion Coefficient 2

1.5 Diffusion Represents a Molecular Event. . 3

1.6 Requirements in Clinical

Diffusion Imaging 4

1.7 Setting the b-Value in Clinical

DW Imaging 4

1.8 Future Trends in Clinical DW Imaging. . . 5 References 5

2 Diffusion-Weighted Imaging of the Normal Brain 7

2.1 Introduction 7

2.2 Adult Brain 7

2.2.2 Diffusion-Weighted Imaging of Gray and White Matter 7

2.2.3 Choroid Plexus 7

2.3 Pediatric Brain 9

2.3.1 Diffusion-Weighted Imaging and ADC of the Pediatric Brain . . 9

2.4 Conclusion 10

References 10

3 Pitfalls and Artifacts of DW Imaging . .

3.1 Introduction

3.2 Influence of ADC and T2

on the DW Appearance

3.2.2 Apparent Diffusion Coefficient Maps

3.2.3 Exponential Images

3.3 Clinical Conditions 12

3.3.1 T2 Shine-through 12

3.3.2 T2 Washout 15

3.3.3 T2 Blackout 16

3.4 Artifacts 18

3.4.1 Eddy Current Artifacts 18

3.4.2 Susceptibility Artifacts 18

3.4.3 N/2 Ghosting Artifact

(Nyquist Ghost) 20

3.4.4 Chemical Shift 20

3.4.5 Motion Artifacts 20

3.5 Conclusion 23

References 23

4 Brain Edema 25

4.1 Characterization and Classification of Brain Edema 25

4.2 Definition and Classification of Cytotoxic Edema 25

4.3 Pathophysiology of Cytotoxic Edema. ... 25

4.3.1 Energy Failure 25

4.3.2 Exci to toxic Brain Injury 27

4.4 Diffusion-Weighted Imaging and Cytotoxic Edema 28

4.4.1 Conditions that Cause Cytotoxic

Edema, and Reversibility 29

4.5 Vasogenic or Interstitial Edema 35

4.5.1 Conditions that Cause

Vasogenic Edema 36

4.6 Conclusion 37

4.6.2 Vasogenic Edema 37

References 37

5 Infarction 39

5.1 Clinical Significance and Therapeutic Considerations for Brain Infarcts 39

5.1.1 Stroke Mimickers 39

5.1.2 Diffusion-Weighted Imaging. ... 39

5.2 Diffusion-Weighted Imaging and Pathophysiology of Cerebral Infarction . . 39

5.3 Apparent Diffusion Coefficient 40

5.3.1 Explanation for Restricted

Diffusion 40

5.4 Time Course of Infarction 40

5.5 Diffusion-Weighted Imaging and ADC Characteristics of Gray and White Matter Ischemia 45

5.5.1 Relative ADC 45

5.6 Reversibility and Treatment 45

5.7 Watershed Infarction 47

5.8 Perfusion Versus Diffusion Imaging 48

5.9 Venous Infarction 48

5.9.1 Predisposing Factors 48

5.9.2 Pathophysiology 48

5.10 Small Vessel Infarcts 50

5.11 Brain Stem and Cerebellar Infarcts 51

5.12 Corpus Callosum Infarcts 52

5.13 Hemorrhagic Infarcts 53

References 54

6 Intracranial Hemorrhage 55

6.1 Introduction 55

6.2 Intraparenchymal Hemorrhages: Appearance and Evolution 55

6.2.1 Hyperacute Hematoma 55

6.2.2 Acute Hematoma 59

6.2.4 Late Subacute Hematomas 62

6.2.5 Chronic Hematomas 62

6.3 Subarachnoid Hemorrhage 62

6.4 Subdural and Epidural Hemorrhages . . . 64

6.5 Intraventricular Hemorrhage 65

6.6 Intra-tumoral Hemorrhage 66

6.7 Hemorrhage Related to Vascular Malformation 67

6.8 Hemorrhage Related to Trauma 68

6.9 Conclusions 68

References 69

7 Vasculopathy and Vasculitis 73

7.1 Definition 73

7.2 Clinical Presentation 73

7.3 Treatment 73

7.4 Vasculitis of the CNS 73

7.4.1 Characterization of

CNS Vasculitis 73

7.4.2 Primary Angitis of the

Central Nervous System 74

7.4.3 Giant Cell (Temporal) Arteritis . . 75

7.4.4 Takayasu's Arteritis

(Aortitis Syndrome) 78

7.4.5 Polyarteritis Nodosa 80

7.4.6 Churg-Strauss Disease 80

7.4.7 Other Small Vessel Vasculitis. ... 80

7.4.8 Collagen Vascular Diseases 80

7.4.9 Infectious Vasculitis 82

7.4.10 Drug-Induced Vasculitis, Including Illicit Drugs 83

7.5 Vasculopathy of the CNS 84

7.5.1 Systemic Lupus Erythematosus . . 84

7.5.2 Moyamoya Disease 86

7.5.3 Sickle Cell Disease 86

7.5.4 Posterior Reversible Encephalopathy Syndrome . . . . 86

7.5.5 Hypertensive Encephalopathy... 87

7.5.6 Preeclampsia/Eclampsia 88

7.5.7 Immunosuppressive Drug-Induced Vasculopathy . . . . 89

7.5.8 Uremic Encephalopathy and Hemolytic Uremic Syndrome ... 91

7.5.9 Thrombotic Thrombocytopenic Purpura 92

7.5.10 Cerebral Amyloid Angiopathy . . . 92

7.6 Conclusion 92

References 93

8 Epilepsy 95

8.1 Definition 95

8.2 Classification 95

8.3 Mechanisms and Pathophysiology of Epilepsy 95

8.4 Magnetic Resonance Imaging of Epilepsy 96

8.4.1 Diffusion-Weighted Imaging in Epilepsy 97

8.4.2 Magnetic Resonance Signal Alterations in Epilepsy 98

8.4.4 Status Epilepticus 100

8.4.5 Cytotoxic Edema in Status Epilepticus 101

8.4.6 Other Imaging Techniques for Epilepsy 103

8.5 Hemiconvulsion-Hemiplegia

Epilepsy Syndrome 103

8.6 Focal Lesion in the Splenium of the Corpus Callosum in Epileptic Patients 103

8.7 Conclusion 103

References 105

9 Demyelinating and Degenerative Disease 107

9.1 Demyelinating Disease 107

9.1.1 Multiple Sclerosis 107

9.1.2 Acute Disseminated Encephalomyelitis 112

9.1.3 Progressive Multifocal Leukoencephalopathy 112

9.2 Degenerative Disease 113

9.2.1 Wallerian or Transneuronal Degeneration 113

9.2.2 Creutzfeldt-Jakob Disease 114

9.2.3 Amyotrophic Lateral Sclerosis . .116

9.3 Conclusion 116

References 117

10 Toxic and Metabolic Disease 119

10.1 Toxic Disease 119

10.1.1 Chemotherapy-Induced Leukoencephalopathy 119

10.1.2 Heroin-Induced Spongiform Leukoencephalopathy 119

10.1.3 Cocaine, Phencyclidine Hydrochloride, Amphetamines and Related Catecholaminergics . 119

10.1.4 Central Pontine Myelinolysis and Extrapontine Myelinolysis. . 122

10.1.5 Wernicke Encephalopathy 123

10.1.6 Marchiafava-Bignami Disease . . 124

10.2 Metabolic Disease 125

10.2.1 Mitochondrial Encephalopathy . 125

10.2.2 Phenylketonuria 126

10.2.3 Other Metabolic Diseases and Leukodystrophies 126

References 129

11 Infectious Diseases 131

11.1 Overview of Brain Infections 131

11.2 Bacterial Brain Abscess 131

11.3 Septic Emboli 132

11.4 Brain Abscess Caused by

Unusual Bacteria 133

11.4.1 Differential Diagnosis 133

11.5 Bacterial Abscess in the

Extra-Axial Space 137

11.5.1 Differential Diagnosis 137

11.6 Bacterial Vasculitis 141

11.7 Toxoplasmosis 141

11.7.1 Differential Diagnosis 143

11.8 Disseminated Aspergillosis 145

11.9 Herpes Encephalitis 145

11.10 Human Immunodeficiency

Virus Infection 146

References 147

12 Trauma 149

12.1 Introduction 149

12.2 Diffuse Axonal Injury 149

12.2.1 Location 149

12.2.2 Computed Tomography and MR Imaging 154

12.2.3 Diffusion-Weighted Imaging . . . 154

12.3 Brain Contusion 154

12.3.1 Location 154

12.3.2 Computed Tomography and MR Imaging 156

12.3.3 Diffusion-Weighted

Imaging Findings 156

12.4 Hemorrhage Related to Trauma 156

12.4.1 Computed Tomography and MR Imaging 157

12.4.2 Diffusion-Weighted Imaging ... 157

12.5 Vascular Injuries 159

References 160

13 Brain Neoplasms 161

13.1 Introduction 161

13.2 Gliomas 161

13.2.1 High-Grade Tumors 161

13.2.2 Peritumoral Infiltration 168

13.2.3 Treatment Response 168

13.3 Epidermoid Tumors and Arachnoid Cysts 169

13.4 Primitive Neuroectodermal Tumors. ... 171

13.5 Meningiomas 172

13.6 Malignant Lymphomas 174

13.7 Craniopharyngiomas 175

13.8 Metastases 176

13.9 Conclusion 178

References 178

14 Pediatrics 181

14.1 Water Content of the Pediatric Brain . . . 181

14.2 Normal Structures 181

14.3 Anisotropy 182

14.4 Infarction and Ischemia 182

14.4.1 Moyamoya Disease 184

14.4.2 Sickle Cell Disease 184

14.4.3 Hypoxic Ischemic Encephalopathy 184

14.5 Trauma 186

14.5.1 Battered Child Syndrome 186

14.5.2 Diffuse Axonal Injury and Brain Contusion 189

14.6 Encephalopathies 189

14.6.1 Mitochondrial Encephalopathy . 189

14.6.2 Acute Necrotizing Encephalopathy 190

14.6.3 Hypertensive Encephalopathy . . 190

14.7 Infections 191

14.7.1 Encephalitis 191

14.7.2 Brain Abscess 193

14.8 Brain Tumor 194

14.9 Dysmyelination and Demyelination 195

14.9.1 Pelizaeus-Merzbacher Disease. . 195

14.9.2 Vanishing White Matter Disease. 196

14.9.3 Metabolic or Toxic Leukoencephalopathies 196

14.9.4 Multiple Sclerosis 197

14.9.5 Osmotic Myelinolysis 197

14.10 Conclusion 199

References 199

15 How to Use This Book 201

Table 1 Differential diagnoses for lesions with a high diffusion signal associated with low ADC

and iso intense T2 signal 202

Table 2 Differential diagnoses for lesions with a high diffusion signal associated with iso-high ADC

and a high intense T2 signal 203

Table 3 Differential diagnoses for lesions with a high diffusion signal associated with a low ADC

and high intense T2 signal 208

Table 4 Differential diagnoses for lesions with an iso diffusion signal associated with a high ADC

and high intense T2 signal 218

Table 5 Differential diagnoses for lesions with a low diffusion signal associated with a high ADC

and high intense T2 signal 219

Table 6 Differential diagnoses for lesions with a low diffusion signal associated with a high ADC

and iso intense T2 signal 221

Table 7 Differential diagnoses for lesions with artifacts 222

Subject Index 225

Basics of Diffusion Measurements by MRI

In collaboration with J.Zhong

Diffusion occurs as a result of the constant movement of water molecules. Water makes up 60-80% of our body weight. The heat associated with our body temperature energizes the water molecules, causing them to "jerk" around randomly. This phenomenon is called "Brownian motion" after the scientist who first described it [1,2]. It can be demonstrated by adding a few drops of ink to a still bucket of water. Initially, the ink will be concentrated in a very small volume, but it will quickly spread out (diffuse) and mix with the rest of the water. The speed of this process of diffusion gives physicists a measure of the property of water. Similarly, if we could put some "magic ink" into the brain tissue and follow its progress, we would gain knowledge about the brain tissue itself, as well as the kind of changes that may occur in the brain when it is affected by various disease processes.

1.2 Diffusion Imaging of the Brain

The brain is complex and full of fibrous,globular and other structures and membranes, which may or may not allow water to move freely. Because water spins will run into constituents of cells of different concentrations in different cellular compartments, they will spread at different rates when labeled with the "magic ink". In addition, they will not behave in the same way when they are moving in different directions. As described below, the former is measured as the diffusion rate, diffusion coefficient, or simply diffusivity, depending on the unit used, and the latter is more formally described as diffusion anisotropy, with a variety of parameters defined [4-7].

1.1 Diffusion Imaging in MR

In the measurement of diffusion by MR, the "magic ink" is created by the magnetic field gradients [3]. When the patient enters the large tunnel of a static magnetic field, nuclear spins (small magnets inside each proton nucleus) are lined up along the direction of the big magnet. Magnetic field gradients of certain duration will then add a smaller magnetic field to spins located in different regions within the tissue. This is similar to marking the spins with "magic ink". By applying another gradient pulse at a later time,in-formation is obtained about how much the spins have spread (diffused) during this time. This is analogous to comparing two snapshots, one taken at the moment when the ink is dropped into the water and one taken later, to obtain information about how the ink has spread in the water. However, the analogy of ink in water and what happens in the brain stops here.

1.3 Magnetic Resonance Principles of Diffusion Imaging

In order to perform diffusion studies, one needs to apply field gradients in addition to the radiofrequen-cy and gradient pulses used for conventional MR imaging. A simplified version of the most commonly used pulse-gradient spin-echo pulse sequence for diffusion imaging is shown in Fig. 1.1. During the time evolution (TE), a pair of field gradients is used to perform "diffusion-encoding." Each gradient in this gradient pair will last a time 8, with strength G (usually in units of mT/m), and the pair is separated by a time A. A more formal analysis will tell us that the intensity of the signal will depend on all these parameters, given by

where ADC is the apparent diffusion coefficient, and b is the gradient factor, sometimes simply called the b-factor. S0 is the signal intensity obtained when no diffusion gradients are used. The diffusion coefficient

Figure 1.1

A typical pulse sequence for diffusion imaging.The shaded areas represent field gradient pulses. DWdiffusion weighted, TE time evolution calculated in this way is usually called "apparent" because it is often an average measure of much more complicated processes in the tissues, as discussed below. The b-factor is related to the gradient parameters 8, G and A (Fig. 1.1), usually in the form b « (dG)2 (A - d / 3), and is set by the experimenter. The formula for the b-factor tells us that we can increase diffusion weighting (DW) by increasing either gradient timing, 8 or A, or gradient strength, G.

Equation 1.1 suggests that there is a reduction in the measured signal intensity when DW is applied, b^0, which can be understood with some simple reasoning. As the diffusing spins are moving inside the field gradient (an additional magnetic field varying in intensity from location to location),each spin is affected differently by the field. The alignment of the spins with each other is thus destroyed. Since the measured signal is a summation of tiny signals from all individual spins, the misalignment, or "dephas-ing", caused by the gradient pulses results in a drop in signal intensity; the longer the diffusion distance, the lower the signal (more dephasing; Fig. 1.2).

1.4 Apparent Diffusion Coefficient

From Eq. 1.1 it can be seen that when a fixed DW b-factor is used, tissues with a higher ADC value produce a lower signal intensity. Since brain cere-brospinal fluid (CSF) contains water that can move around freely, its ADC value is much higher than that of other brain tissues (either gray matter or white matter),which contain many more cellular structures and constituents. Consequently, in a DW image one typically sees dark CSF space (pronounced dephasing) and brighter tissue signals (less dephasing). It is also clear from Eq. 1.1 that if we collect a series of DW images with different b-values, we can calculate according to the expression for every pixel and obtain a parametric map of ADC values. The result is sometimes referred to as an ADC map. The calculated ADC map would have image pixel intensities reflecting the strength of diffusion in the pixels. Regions of CSF will therefore have higher intensity than other brain tissues - a reversal of DW images. There are several reasons why it is sometimes desirable to calculate an ADC map instead of just using DW images. One is the so-called T2-shine-through effect, which will be discussed in a later chapter. It can also be noted that S0 in Eq. 1.1 is equal to the signal when no DW is used.

Figure 1.2

Effects of gradients on diffusing spins. Diffusion in the gradient causes dephasing of spins and therefore reduction in the measured signal intensity

Figure 1.1 suggests that this is actually the same as would be obtained from a simple spin-echo sequence. In most clinical scanners, a long TE time (tens of milliseconds) is needed to accommodate the diffusion pulses, so S0 is often T2-weighted.

1.5 Diffusion Represents a Molecular Event

Even though an image pixel size in the order of millimeters is used in most clinical MR imaging, the information provided by diffusion imaging reflects cellular or molecular events in much smaller scales. This is because the molecular diffusion process is highly modulated by these events. It can be shown that water spins diffuse about tens of micrometers during a typical MR imaging measurement time, which coincides with the dimension of typical cellular structures. If spins experience minimal obstruction from cellular structures during this time (such as for spins in the CSF space), the measured diffusion is "free" and "isotropic", and ADC is just the intrinsic molecular diffusion coefficient. On the other hand, when diffusing spins run into cellular constituents and membranes, the value of ADC will be reduced when compared with the value in free space. What happens at the cellular level is represented schematically in Fig. 1.3. For patients with neurological abnormalities that change the water distribution in various cellular compartments, or change the ability of water to pass through cell membranes, the measured ADC values will also be altered [4-7]. Therefore the MR diffusion measurement offers a unique opportunity to obtain information about morphology otherwise inaccessible to conventional MR imaging methods. A wide range of pathological conditions can be explored with water diffusion measurements, as described later in this book. The measured ADC may also vary depending on the duration of the diffusion process, the direction in which diffusion is measured, and other factors. For diffusion in an anisotropic environment (such as in brain white matter, where bundles of axons with myelin layers wrapped around them make diffusion along the bundle much easier than across the bundle), diffusion becomes more complicated and a complete description of the process relies on what is called tensor analysis [8,9].

Figure 3.1

When water spins are diffusing among cellular structures, depending on the mean displacement (<r2>) during the measurement time and the size of the cellular structure, their behavior can be quite different.Water inside a non-permeable cell (top and bottom left) experiences restriction or hindrance to diffusion. Diffusion barrier effects are minimal for water inside a permeable cell,or in a cell that is much larger than the mean displacement during diffusion (top middle and right, and bottom right)

1.6 Requirements in Clinical Diffusion Imaging

In a clinical environment, certain requirements are imposed for diffusion studies. A reasonable imaging time is often limited to several minutes for each type of measurement (T1 W, T2 W, diffusion, and others). Multiple slices (15-20) are required to cover most of the brain. A good spatial resolution (~5-8 mm thick, 1-3 mm in-plane) is required. A reasonably short TE (120 ms) to reduce T2 decay, and an adequate diffusion sensitivity (ADC ~0.2-1x10-3 mm2/s for brain tissues) are also needed. However, most essential is the almost complete elimination of sensitivity to subject motion during scanning. The best compromise so far in most clinical practices of diffusion imaging is the use of the multi-directional (x,y,z), 2 b-factor (b=0, and b~1/ADC) single-shot echo-planar imaging technique. Sometimes fluid attenuation with inversion recovery (FLAIR) is used to eliminate signal in the highly diffusive CSF space. Separation from relaxation effects is achieved with calculation of ADC

instead of just using DW, and elimination of anisotropic diffusion is achieved by averaging the diffusion measurements from three orthogonal directions.

1.7 Setting the b-Value in Clinical DW Imaging

In a clinical setting it is advisable to maintain the same b-value for all examinations, making it easier to learn to interpret these images and become aware of the appearance of findings in various disease processes. The studies and discussions presented in this book are limited to DW imaging using b-factors of 0 and 1,000. An upper b-factor around 1,000 has been available for most clinical scanners until now and DW imaging at these standard values has been shown to be a sensitive tool in detecting and delineating restricted diffusion, e.g. in acute ischemic lesions of the brain. However, this technique has become clinically important in many other disease processes, which will be discussed in this book.

1.8 Future Trends in Clinical DW Imaging

Newer DW imaging techniques are using even higher b-values: 8.000 and more. Some recent articles that explore the use of higher b-values imply that they will simplify clinical diffusion imaging [10]. The increased b-values may free up routine DW imaging from its most pressing problem, "T2 shine-through". At high b-values more attention will be focused on the actual physiological basis of restricted and facilitated diffusion. Clearly, much of the advantage of increased b-values may lie not with the diagnosis of lesions with restricted diffusion, especially acute in-farcts, but with allowing a more complete understanding of other types of diseases.

The benefits of improved diffusion contrast at high b values come with the complication of prescription dependent measures of apparent diffusion. The ADC is conventionally derived from images taken at two different b-values. Because tissues are described by fast and slow components, the results of a two-point measurement will depend on the specific b-values chosen. If the lower b-value is set to 0 (a T2-weighted image) and the upper value is allowed to vary, the ADC will vary as a function of the upper value. Specifically, one would expect the measured ADC to decrease as the upper b-value increases.

Another area of DW imaging that will evolve over the next few years is diffusion tensor imaging, which is becoming available in many modern clinical scanners. When these and other techniques become more accessible and technically more mature, they may provide more specific measurements.

References

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Diffusion-Weighted Imaging of the Normal Brain

In collaboration with A. Hiwatashi and J.Zhong

2.1 Introduction

Diffusion-weighted (DW) images are usually obtained in three orthogonal orientations using spinecho type single-shot DW echo-planar imaging with b-values around 0 and 1,000 s/mm2. These three planes are combined into isotropic DW images, and apparent diffusion coefficient (ADC) maps are calculated on a pixel-by-pixel basis (Fig. 2.1).To avoid misinterpretations, it is important to recognize the normal findings on DW images and ADC maps.

2.2 Adult Brain

2.2.1 Low Signal in Basal Ganglia

Isotropic DW imaging in adult brain often shows low signal intensity in the basal ganglia (Fig. 2.1). This low signal is caused by normal iron deposition. The hypointensity on DW images of these areas is essentially related to T2 contrast, which is also shown on b0 images. ADC maps usually show the areas as iso-intense, but it can be hyper- or hypointense depending on the paramagnetic susceptibility artifact of iron deposition.

2.2.2 Diffusion-Weighted Imaging of Gray and White Matter

Gray matter on DW images is generally hyperintense when compared with white matter. ADC of gray (0.76±0.13x 10-3 mm2/s) and white matter (0.77± 0.18 x 10-3 mm2/s) are, however, identical in the adult brain [1]. There are several reports about ADC increasing with age [2-7], but this increase is minimal and has been observed in all parts of the brain. It is usually more apparent in the white matter and lentiform nucleus than in the rest of the brain. Focal areas of DW hyperintensities are often seen in posterior limbs of internal capsule, corticospinal tracts, medial lemniscus and the decussation of the superior cerebellar peduncles (Fig. 2.1). These DW hyperintensities are caused by T2 contrast and represent normal findings without clinical significance. ADC maps are usually isointense in these areas.

2.2.3 Choroid Plexus

The choroid plexus occasionally shows prominent hyperintensity on DW imaging associated with mild elevation of ADC. In these situations the ADC is often higher than in white matter, but lower than in cere-brospinal fluid. The high DW signal is believed to represent gelatinous cystic changes of the choroid plexus, which can occur with age (Fig. 2.2).

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