European Journal of Radiology, 14 (1992) 0
1992 Elsevier
EURRAD
Science Publishers
83-96 83
B.V. All rights reserved. 0720-048X/92/$03.50
00250
Magnetic resonance in neurological disorders J. Valk Department of Diagnostic Radiology, Free University Hospital, Amsterdam,
Key words: Magnetic resonance,
neurology; Neurology,
The Netherlands
MR
Introduction The major role played by MR in neurological disorders is the result of the great number of tissue and machine parameters involved in the formation of the MR data, as compared to CT (Tables 1 and 2). The great variety of parameters involved in MR accentuates the still present possibilities for improvements in the next years. The most flexible tool of MR TABLE 1 CT Parameters Machine
Tissue
a
Kilovoltage Miliamperesls Slice thickness Gantry tilt (restricted) Field of view
Electron density -
Fig. 1. (a and b) Two transverse Tl-weighted IR images in a baby 3 months of age, showing the myelination with high signal intensity. Myelination is present shortly after birth in the cerebellum, the brain stem and spreading from there in a definite pattern. At the age of three month there is myelination visible in the post- and precentral gyrus, spreading from there in ventral and dorsal direction.
Iodine containing
Contrast
media
Postprocessing
b
TABLE 2 MR parameters Machine
Tissue
Pulse sequences* Multiplanar 2D or 3D acquisition Slice thickness Field of view Flow compensation Flow encoding Diffision encoding Presaturation
Relaxation times Proton density Paramagnetics Magnetic susceptibility Diffusion Perfusion Paramagnetic or Supraparamagnetic Contrast media
Postprocessing *Wide range of choices. Address for reprints: Prof. Dr. J. Valk, Department of Diagnostic Radiology, Free University Hospital, de Boelelaan 1007, 1081 HV Amsterdam, The Netherlands
a
b
Fig. 2. (a and b) Transverse slices in a normal adult at 2.0 Tesla on T2-weighted images showing the low signal intensity of the pallidum, the substantia nigra and the nucleus ruber. The lower signal intensity results from deposition and biochemical distribution of iron. This pattern is not present at birth but evolves gradually until the second half of the second decade.
a
b a
Fig. 3. (a and b) Example of a congenital malformation with large encephalocele. The Tl-weighted images provide much of the necessary information. Note how the brain stem and the temporal lobes seem to have been lifted by the encephalocele.
machines consists of the pulse sequences. In recent years it has been shown that better and faster results often can be obtained by the use of sometimes very complex pulse sequences. Without understanding the basic principles underlying the effects of these pulse sequences the resulting images can hardly be understood. For a correct interpretation it is also necessary to understand the side-effects of the techniques of arte-
a
b
Fig. 4. (a and b) Baby boy of 3 months of age. A transverse T2weighted SE image at the level of the circle of Willis and a sagittal T2-weighted GE image. The transverse image (a) shows the enlarged vessels of the circle of Willis. The sagittal image (b) shows the aneurysm of the vein of Galen and the also enlarged anterior cerebral artery.
fact reduction, the physics behind the quantitative measurement of flow, the impact on the image of the various types of reconstruction (real, imaginary, magnitude and phase), the relationship between the degree of nutation of the magnetization along the Z-axis (flipangle) and the Tl- or T2-weighting of the image, changes in the image as the consequence of the entry phenomenon and even echo rephasing, and the effects
b
Fig. 5. (a and b) Two Tl-weighted (IR) transverse images, at the level of the foramina of Monro (a) and at the level of the pons. The first ima ge shows the involvement of the corpora geniculata (cg) and the white matter around the occipital horns, sparing the U-fibers (u) in this case of X-linked adrenoleukodystrophy. The image through the pons shows the typical affliction of pontine tracts in this disorder.
a a
b
Fig. 6. (a and b) Two transverse T2-weighted SE images showing the distinct features of a vacuolating myelinopathy, caused by splitting of the bilayer myelin membranes. The affected white matter shows some swelling and stretching of the gray matter leading to a highly characteristic image seen in Canavan’s disease, idiopathic spongy sclerosis and, more focal, in some of the other amino and organic acidopathies.
of paramagnetic and supraparamagnetic compounds on the image, as illustrated in vivo by the signal changes occurring in hemorrhages over time. The practice of presenting the images to clinicians as either Tl-, T2- or proton-density weighted is an oversimplification and may lead to misunderstanding. Postprocessing is mentioned in both of the tables. Much more data can be extracted from the images or spectroscopic data with appropriate application of postprocessing methods. Neither CT nor MR should be read from hard
a
b
Fig. 8. (a and b) Boy, 6 years of age. Sagittal Tl-weighted SE images without (a) and with(b) Gadolinium. The tumor in the diencephalon enhances clearly. This may be helpful in selecting a site for biopsy.
a
b
Fig. 9. (a and b) Baby girl of 3 weeks. Only few tumors are highly characteristic. The coronal (a) and sagittal (b) Tl-weighted SE images show an intraventricular tumor compared of rounded structures, containing fluid with high protein content and a stroma linking the structures together. There is also a clear expansion of the ventricle. The diagnosis is plexus papilloma, with overproduction of CSF.
b
Fig. 7. (a and b) Vacuolating myelinopathy can also be seen in patients with congenital muscular dystrophy, here presented in a parasagittal Tl-weighted SE image (a), and a T2-weighted SE transverse image (b), both showing the features of this kind of disorder. The occipital lobes are in this case less involved than the frontal and parietal lobes.
a
b
Fig. 10. (a and b) Neurotibromatosis type II with bilateral acustic neurinomas; extramedullary tumors and multiple meningeomas, as shown on these Tl-weighted SE, Gd-enhanced, sagittal and transverse images.
86
a
d
b
e
f
Fig. 11. (a-f) Tl-weighted SE (a-c) and T2-weighted SE (d-f) transverse images in a newborn child with asphyctic episodes during birth. damage. In the frontal and parietal lobes, areas are seen with a too low signal The images show a peculiar pattern of posthypoxic-ischemic intensity on Tl-weighted, a too high signal on TZweighted images. In the parietal area necrosis has occurred.
copies. The futed window and level setting alone will obliviate a lot of the information present in the image. MR spectroscopy, in particular the calculation of absolute concentrations of metabolites, is unthinkable without postprocessing. MRI sensitivity and specificity The unique sensitivity of MR is mentioned by many authors. Specificity is considered usually to be much lower. The terms sensitivity and specificity in this respect are not to be confused with the epidemiological terms sensitivity, meaning the number of true positives identified’by a test, and specificity, meaning the number
of true negatives identified by the test, as percentage of respecti ely the total number of patients with or without the dis kase. Here sensitivity relates to the detection threshold of (any) abnormality in the test, the MR scan, specificity to the relationship of the identified abnormalities to a certain diagnostic category. Sensitivity in this sense is the result of the tissue and machine parameters involved in the formation of the MR image, of which the latter can be manipulated to provide optimal contrast conditions between tissues. Specificity in this sense also depends on many factors. If a number of diseases have the same pathomorphological expression on MR, the specificity of MR is limited to the identification of this group. If on the
87
a
b
Fig. 12. (a and b) MR has the unique possibility to visualize laminar cortical necrosis as demonstrated in this image of a 2-year-old child with spasticity, mental retardation and epileptic seizures. There is no periventricular abnormality in this patient. In the cortex bands of high signal intensity are seen on the T2-weighted images, better seen in the zoomed image (b).
other hand, more detailed analysis of the images leads to the identification of structural elements that can distinguish between the different entities within the group, the reading of the MR image becomes more specific. For this purpose a learning process (experience) is necessary to identify changes in the images as related to a specific neuropathological disorder. Examples are the
a
b
TZprevalent relaxation time shortening in the basal ganglia, substantia nigra, nucleus ruber, nucleus dentata as the result of mineral deposition and its relation to diseases of the extrapyramidal system [ 11. Or the Tl-prevalent relaxation time shortening of the basal ganglia on Tl-weighted images in hepatocerebral syndromes and some other toxic syndromes [2,3]. These
d
Fig. 13 (a-d) Tl-weighted SE images of a term born neonate in a poor clinical condition and with hyperechogenic, poorly demarcated areas on US. MR shows intraventricular hemorrhage, with diffuse extensions in the parenchyma. The images also show loss of gray-white matter contrast, indicative of a poor cerebral perfusion.
88
15b Fig. 14 MR is the imaging modality of first choice in partial refractary epilepsy. In this parasagittal TZ-weighed SE image the frontobasal temporal gliosis in such a case is beautifully shown (arrow). CT was repeatedly negative.
and
Fig. 15. (a and b) Transverse proton density (a) and TZ-weighted SE images in a case of refractory partial epilepsy. Apart from the lesion in the hippocampus-uncus are (arrow in b) there is absence of the normal myelination pattern of the left temporal lobe, suggestive of diffuse hamartomatous changes (arrows in a) (brought to my attention by Linda Meiners, Utrecht).
pathophysiological, physical, biochemical and pathomorphological facts have to be learned and understood. The acquired knowledge will lead to a dramatic improvement of the specificity of MRI. We have demonstrated this in a pattern recognition programme for MR of white matter diseases [4]. For this purpose 42 structural elements of the MR images, relevant to the distinction of the various subtypes of WMD’s, were identified. In 277 patients with known WMD these elements were analysed, scored according to a protocol and fed into a database. The frequency of occurrence of each MR abnormality was assessed per disease category and thus the pattern of abnormalities characteristic for each disease category emerged. Now the programme can be used in the reversed direction. When fed data about MR abnormalities in a new case, the computer produces a differential diagnosis with MR probability and 95 yOconfidence intervals per diagnosis. Such a programme could be developed for other categories, such as congenital abnormalities, gray matter disorders, spinal pathology etc. It will not compete with the accuracy, flexibility or combining power of an experienced MR reader; the programme, however, could serve the less experienced and be a valuable teaching aid. This programme has also prompted further research into recognizable patterns in rare disorders of which too few cases are present in the database to establish frequency patterns of
abnormalities and useful confidence intervals. In this way we were engaged in the description of patterns in peroxisomal disorders [5] followed by patterns in organic and aminoacidopathies [ 61. This latter category poses extreme difficulties for the identification of patterns. This is the result of the various locations in the subcellular structures of the enzymatic deficit, peroxisomal, mitochondrial or cytoplasmic and the multitude of biochemical pathways included in these metabolic disorders. The organic and aminoacidopathies are therefore very variable in their clinical expression and in the morphological and biochemical abnormalities as expressed in the MR images and, at least in some cases, in MR spectroscopy. We have so far identified live patterns. These patterns result from the various consequences of the enzyme deficit within the organelle, with the disturbance of, for example, the oxidative energy supply, with synthesis of certain proteins, vitamins, or neurotransmitters, or with the action of a toxic product generated due to the lacking enzyme and the production of an exces of organic acids. Undoubtedly more patterns will emerge with better understanding of analogies and differences between the various disorders. The patterns identified until now are: 1. Prevalent afRiction of the arcuate fibers, sparing the cerebral white matter, more general, as in Canavan’s disease [7], or more focal, as in 2-hydroxyglutaric aciduria.
89
a
b
C
d
Fig. 16. (a-d) Unilateral encephaloclastic schizencephaly. Note that the clefi on the Tl-eighted SE (a) and Tl-weighted IR (b) images is surrounded by a thick layer of gray matter. This, however is the result of the loss of white matter and severe gliotic retraction in this area. The TS-weighted SE image (c) shows some hyperintense areas in the left frontal lobe, which can be mistaken for myelination. The proton density (d) image makes clear that this is caused by gliosis as an extension of a periventricular leukomalacia.
2. Involvement of the basal ganglia together with bilatera1 temporal arachnoid cysts and fronto-temporal atrophy, as in glutaric aciduria type I and methylmalon acidura.
3. Periventricular white matter affliction, as in phenylketonuria [ 81. white matter disease with calcili4. Periventricular cations, as in some phenylketonuria variants [9].
Fig. 17. MR angiography will be applied on a large scale in the years to come and will replace in neurology and neurosurgery angiography.
nearly all diagnostic
Fig. 18. (a and b) Nutritional deficiencies and subacute intoxications may lead to pecular abnormalities. These images are of a 7-year-old boy with a long lasting diet of only french fries (without mayonnaise) and who was admitted with lowered consciousness, desorientation, changed speech pattern. He was shown to have a severe vitamine B complex deficiency. The Tl-weighted (IR) and T2-weighted SE images at the same level show the abnormalities in the thalamus. Note that the IR image allows more easily localization of the lesions in the thalamus.
a
b
Fig. 19. (a and b) Wernicke’s encephalopathy leads to a specific pattern of involvement of brain structures, very similar to what is seen in Leigh’s disease. The T2-weighted transverse images show the lesions in the basal ganglia, predominantly on the right side, the involvement of the mammilary bodies and the peri-aqueductal gray matter, the latter probably causing the hydrocephalus.
5. Generalized supratentorial edema, together with a toxic edema of the brain stem and posterior fossa, with possible evolution towards atrophy, as in maple syrup urine disease [ lo]. In this group of patients one can expect other anomalies, local atrophy, micro- or macrocephaly, subdural effusions or arachnoid cysts, corpus callosum agenesis and so on. Such an analysis of patterns is also prepared for peroxisomal, lysosomal [ 1 l- 131 and mitochondrial disorders [ 14,151. The given examples show that specificity is strongly dependent on the training and experience of the reader of the images. MR superior to CT It has become evident in the last live years that the yield of MR in a number of diagnostic categories is so much higher than that of other imaging modalities, in particular CT, that MR should be the first choice when an imaging modality is required. In fact, in many of these categories no other imaging modality is requested. Mentioned are here: Normal maturation of the brain (myelination, gyration, corpus callosum formation, iron deposition in basal ganglia) [ 161, congenital anomalies of brain and spinal cord [ 171, acquired and hereditary white matter disorders, toxic encephalopathies, refractary partial epilepsy [ 18-201 sellar and parasellar lesions and neuroendocriene disorders, posthypoxic-ischemic en-
a
b
Fig. 20. (a and b) T2-weighted SE transverse images in a 9-year-old boy with delayed development of speech and language. The medical history reports asphyxia during birth. Neurological examination was normal. MR shows selective involvement of the thalamus (arrows).
cephalopathy in infants older than 3 months, intra- and extra-axial tumours, leptomeningeal afllictions 121,221, postoperative, postradiotherapeutic, postchemotherapeutic conditions of the brain, and all lesions of the spine. In some conditions a special role of MR has emerged, such as the therapy monitoring in multiple sclerosis [23]. Other special applications of MR are also unequalled. MR angiography is rapidly developing as a means of obtaining extra information in certain conditions and will replace much of the diagnostically performed angiography. Quantitative flow measurements in the aqueduct and spinal canal will help to understand CSF dynamics in physiological and pathological conditions. Anisotropically restricted diffusion imaging allows a different view on white matter tracts during progress of myelination and white matter disorders [24,25]. Magnetization transfer imaging, realised by off-frequency irradiation of the investigated structures, extracts information from bound protons, otherwise not visible. These new techniques demand still validation in clinical practice but already have shown their potential. In preterm neonates neurosonography plays an important role as a screening device for intracranial hemorrhagic or leukomalacic conditions. The versatility of the ultrasonographic equipment will guarantee this place for the years to come. MR, however, has proved to be of great value even in this category and is uniquely capable of demonstrating selective neuronal loss in cortical laminar necrosis, Sommer’s sector necrosis, necro-
Fig. 21. (a and b) Series of five TZ-weighted SE and one IR (b), images showing the multitude of lesions seen in a mycoplasm infection. Some of these : lesions are symmetrical, for example in the middle cerebellar peduncle, others are spread through the brain. The IR shol NS the inhomogeneity of the lesions (arrow in b) clearer than the T2-weighted SE.
92
Fig. 22. Sagittal Tl-weighted gradient echo image of the cervical spine showing beautifully the herniated disc at the C3-C4 level.
sis of the subiculum, of thalamic nuclei and of the Purkinje cells [ 261. There is still a clear role for CT in analysis of bony structures, in the diagnosis of acute hemorrhagic conditions, in the work up of facial anomalies, in acute traumatology of head and spine, postoperative controls, shunt controls in hydrocephalus, and so on. A series of illustrations demonstrates the diagnostic power of MRI (Figs. l-25). MR spectroscopy (MRS) Though some clinical applications start to emerge, MRS is still very much a research tool. The progress made, however, in the last few years is considerable. Volume-selection is now possible on commercial machines, the required minimal volumen for ‘H spectroscopy has decreased considerably, chemical shift imaging will be a routine procedure in a relatively short time. The claim of positron emission tomographists that PET looks at metabolism and MRS at metabolites more and more proves to be a sophism. First of all in disorders of muscle metabolism, but gradually also in other organs, liver, heart and brain, MRS enables analysis of metabolic chains and the effect of interventions. MRS has the potential to identify the anabolic or catabolic products of a certain metabolite. This comes with the advantage that MRI and MRS can be per-
formed on the same machine, so that no adaptations of the frame of reference are necessary to combine image data with chemical shift images of metabolites. MR spectroscopy is a demanding technique and the interpretation of the results is only possible with consideration of all technical details of both acquisition and postprocessing techniques. For example: In the analysis of the ‘H-spectra of the brain of patients with hepatocerebral syndromes longer echotimes (135 ms or more) do not show the myo-inositol peak, which is visible at shorter echotimes (20 ms or less). This peak shows the most constant abnormality in the spectrum in this kind of intoxication [27,28]. As in MR imaging brain maturation is an important factor in MR spectroscopy. Normal values of 31P and ‘H-MR spectroscopy of all ages with different techniques have to be collected. It is not sufficient to compare the data of a patient with one or two age matched controls, as is often done. The variation in normal individuals is of such a magnitude that normal values have to be acquired from a statistical adequate number of normal individuals per age group, defining the normal value and the standard variation. We performed such a study [29] in normal infants, children and adolescents with regard to ‘H and 31P spectroscopy. The influence of brain maturation on 31P and ‘H spectra was clearly shown, as was the fact that the effects of maturation of the brain are longer noticeable in MRS than in MRI. The ‘H spectra were made with a TE of 270 ms and therefore metabolites with a much shorter T2 are not visible in the spectra. Since ‘H spectroscopy with TEs of 20 ms and less is now feasible, normal values for these TEs have to be obtained. MRS can be partially used in the differentiation between demyelinating and neuronal disorders [ 301. For that purpose 35 patients with a degenerative cerebral disorder, 24 with a demyelinating disorder, 11 with a neuronal disorder, were examined. Four grades of demyelination and 3 grades of cerebral atrophy were graded on basis of MRI criteria. The spectroscopic data were compared with normal values. A statistically significant decrease of the PDE//?-ATP was found with an increasing degree of demyelination. The spectral abnormalities appeared to be synchronous with the abnormalities in the images. With an increasing degree of cerebral atrophy a decreasing NAA/Cr was found. Also this finding was statistically significant. This decrease in NAA/Cr, however, occurred before the MR images showed signs of cerebral atrophy in patients with a neuronal disorder. This last phenomenon was recently also described in patients with the AIDS dementia complex (Fig. 26a-d).
93
Fig. 23. (a-d) MR Tl-weighted
SE images of the cervico-thoracic spine, without (a and b) and with contrast (c and d). The cord is swollen is caused by a cyst like structure with rounded upper pole. After contrast there is enhancement of a di stinct nodule within the cyst, with some? linear structures with low signal intensities, probably vessels. Diagnosis, hemangioblastoma, confirmed by histology. Complete recovery after surgery.
ove1 . the whole length and the distension
Conclusion Never before radiologists and clinicians possessed such a powerful diagnostic tool. This tool is at the same time demanding a great investment of its users, especi-
ally in the effort to acquire the knowledge and experience to extract the maximum of the wealth of data offered by both MRI and MRS.
e
f
Fig. 24. (a 0 Series of sagittal images of the cervico-thoracic spine, proton density and T2-weighted SE (a and b) where a lesion Mrith s:omelwhat prot jably :r sign l;i, ntensity is first visible on the T2-weighted image (arrow in b). After Gd-DTPA there is clearly enhancement of a lez with cereb lral necrosis at the level of Th2-3. The enhanced area has irregular borders. In the Tl-weighted SE coronal images 01.the lung also :nh ancing lesions are seen, with the same pattern. The diagnosis in this ll-year-old young man was Wegener’s dise :ase.
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1992 Elsevier
EURRAD
Science Publishers
83-96 83
B.V. All rights reserved. 0720-048X/92/$03.50
00250
Magnetic resonance in neurological disorders J. Valk Department of Diagnostic Radiology, Free University Hospital, Amsterdam,
Key words: Magnetic resonance,
neurology; Neurology,
The Netherlands
MR
Introduction The major role played by MR in neurological disorders is the result of the great number of tissue and machine parameters involved in the formation of the MR data, as compared to CT (Tables 1 and 2). The great variety of parameters involved in MR accentuates the still present possibilities for improvements in the next years. The most flexible tool of MR TABLE 1 CT Parameters Machine
Tissue
a
Kilovoltage Miliamperesls Slice thickness Gantry tilt (restricted) Field of view
Electron density -
Fig. 1. (a and b) Two transverse Tl-weighted IR images in a baby 3 months of age, showing the myelination with high signal intensity. Myelination is present shortly after birth in the cerebellum, the brain stem and spreading from there in a definite pattern. At the age of three month there is myelination visible in the post- and precentral gyrus, spreading from there in ventral and dorsal direction.
Iodine containing
Contrast
media
Postprocessing
b
TABLE 2 MR parameters Machine
Tissue
Pulse sequences* Multiplanar 2D or 3D acquisition Slice thickness Field of view Flow compensation Flow encoding Diffision encoding Presaturation
Relaxation times Proton density Paramagnetics Magnetic susceptibility Diffusion Perfusion Paramagnetic or Supraparamagnetic Contrast media
Postprocessing *Wide range of choices. Address for reprints: Prof. Dr. J. Valk, Department of Diagnostic Radiology, Free University Hospital, de Boelelaan 1007, 1081 HV Amsterdam, The Netherlands
a
b
Fig. 2. (a and b) Transverse slices in a normal adult at 2.0 Tesla on T2-weighted images showing the low signal intensity of the pallidum, the substantia nigra and the nucleus ruber. The lower signal intensity results from deposition and biochemical distribution of iron. This pattern is not present at birth but evolves gradually until the second half of the second decade.
a
b a
Fig. 3. (a and b) Example of a congenital malformation with large encephalocele. The Tl-weighted images provide much of the necessary information. Note how the brain stem and the temporal lobes seem to have been lifted by the encephalocele.
machines consists of the pulse sequences. In recent years it has been shown that better and faster results often can be obtained by the use of sometimes very complex pulse sequences. Without understanding the basic principles underlying the effects of these pulse sequences the resulting images can hardly be understood. For a correct interpretation it is also necessary to understand the side-effects of the techniques of arte-
a
b
Fig. 4. (a and b) Baby boy of 3 months of age. A transverse T2weighted SE image at the level of the circle of Willis and a sagittal T2-weighted GE image. The transverse image (a) shows the enlarged vessels of the circle of Willis. The sagittal image (b) shows the aneurysm of the vein of Galen and the also enlarged anterior cerebral artery.
fact reduction, the physics behind the quantitative measurement of flow, the impact on the image of the various types of reconstruction (real, imaginary, magnitude and phase), the relationship between the degree of nutation of the magnetization along the Z-axis (flipangle) and the Tl- or T2-weighting of the image, changes in the image as the consequence of the entry phenomenon and even echo rephasing, and the effects
b
Fig. 5. (a and b) Two Tl-weighted (IR) transverse images, at the level of the foramina of Monro (a) and at the level of the pons. The first ima ge shows the involvement of the corpora geniculata (cg) and the white matter around the occipital horns, sparing the U-fibers (u) in this case of X-linked adrenoleukodystrophy. The image through the pons shows the typical affliction of pontine tracts in this disorder.
a a
b
Fig. 6. (a and b) Two transverse T2-weighted SE images showing the distinct features of a vacuolating myelinopathy, caused by splitting of the bilayer myelin membranes. The affected white matter shows some swelling and stretching of the gray matter leading to a highly characteristic image seen in Canavan’s disease, idiopathic spongy sclerosis and, more focal, in some of the other amino and organic acidopathies.
of paramagnetic and supraparamagnetic compounds on the image, as illustrated in vivo by the signal changes occurring in hemorrhages over time. The practice of presenting the images to clinicians as either Tl-, T2- or proton-density weighted is an oversimplification and may lead to misunderstanding. Postprocessing is mentioned in both of the tables. Much more data can be extracted from the images or spectroscopic data with appropriate application of postprocessing methods. Neither CT nor MR should be read from hard
a
b
Fig. 8. (a and b) Boy, 6 years of age. Sagittal Tl-weighted SE images without (a) and with(b) Gadolinium. The tumor in the diencephalon enhances clearly. This may be helpful in selecting a site for biopsy.
a
b
Fig. 9. (a and b) Baby girl of 3 weeks. Only few tumors are highly characteristic. The coronal (a) and sagittal (b) Tl-weighted SE images show an intraventricular tumor compared of rounded structures, containing fluid with high protein content and a stroma linking the structures together. There is also a clear expansion of the ventricle. The diagnosis is plexus papilloma, with overproduction of CSF.
b
Fig. 7. (a and b) Vacuolating myelinopathy can also be seen in patients with congenital muscular dystrophy, here presented in a parasagittal Tl-weighted SE image (a), and a T2-weighted SE transverse image (b), both showing the features of this kind of disorder. The occipital lobes are in this case less involved than the frontal and parietal lobes.
a
b
Fig. 10. (a and b) Neurotibromatosis type II with bilateral acustic neurinomas; extramedullary tumors and multiple meningeomas, as shown on these Tl-weighted SE, Gd-enhanced, sagittal and transverse images.
86
a
d
b
e
f
Fig. 11. (a-f) Tl-weighted SE (a-c) and T2-weighted SE (d-f) transverse images in a newborn child with asphyctic episodes during birth. damage. In the frontal and parietal lobes, areas are seen with a too low signal The images show a peculiar pattern of posthypoxic-ischemic intensity on Tl-weighted, a too high signal on TZweighted images. In the parietal area necrosis has occurred.
copies. The futed window and level setting alone will obliviate a lot of the information present in the image. MR spectroscopy, in particular the calculation of absolute concentrations of metabolites, is unthinkable without postprocessing. MRI sensitivity and specificity The unique sensitivity of MR is mentioned by many authors. Specificity is considered usually to be much lower. The terms sensitivity and specificity in this respect are not to be confused with the epidemiological terms sensitivity, meaning the number of true positives identified’by a test, and specificity, meaning the number
of true negatives identified by the test, as percentage of respecti ely the total number of patients with or without the dis kase. Here sensitivity relates to the detection threshold of (any) abnormality in the test, the MR scan, specificity to the relationship of the identified abnormalities to a certain diagnostic category. Sensitivity in this sense is the result of the tissue and machine parameters involved in the formation of the MR image, of which the latter can be manipulated to provide optimal contrast conditions between tissues. Specificity in this sense also depends on many factors. If a number of diseases have the same pathomorphological expression on MR, the specificity of MR is limited to the identification of this group. If on the
87
a
b
Fig. 12. (a and b) MR has the unique possibility to visualize laminar cortical necrosis as demonstrated in this image of a 2-year-old child with spasticity, mental retardation and epileptic seizures. There is no periventricular abnormality in this patient. In the cortex bands of high signal intensity are seen on the T2-weighted images, better seen in the zoomed image (b).
other hand, more detailed analysis of the images leads to the identification of structural elements that can distinguish between the different entities within the group, the reading of the MR image becomes more specific. For this purpose a learning process (experience) is necessary to identify changes in the images as related to a specific neuropathological disorder. Examples are the
a
b
TZprevalent relaxation time shortening in the basal ganglia, substantia nigra, nucleus ruber, nucleus dentata as the result of mineral deposition and its relation to diseases of the extrapyramidal system [ 11. Or the Tl-prevalent relaxation time shortening of the basal ganglia on Tl-weighted images in hepatocerebral syndromes and some other toxic syndromes [2,3]. These
d
Fig. 13 (a-d) Tl-weighted SE images of a term born neonate in a poor clinical condition and with hyperechogenic, poorly demarcated areas on US. MR shows intraventricular hemorrhage, with diffuse extensions in the parenchyma. The images also show loss of gray-white matter contrast, indicative of a poor cerebral perfusion.
88
15b Fig. 14 MR is the imaging modality of first choice in partial refractary epilepsy. In this parasagittal TZ-weighed SE image the frontobasal temporal gliosis in such a case is beautifully shown (arrow). CT was repeatedly negative.
and
Fig. 15. (a and b) Transverse proton density (a) and TZ-weighted SE images in a case of refractory partial epilepsy. Apart from the lesion in the hippocampus-uncus are (arrow in b) there is absence of the normal myelination pattern of the left temporal lobe, suggestive of diffuse hamartomatous changes (arrows in a) (brought to my attention by Linda Meiners, Utrecht).
pathophysiological, physical, biochemical and pathomorphological facts have to be learned and understood. The acquired knowledge will lead to a dramatic improvement of the specificity of MRI. We have demonstrated this in a pattern recognition programme for MR of white matter diseases [4]. For this purpose 42 structural elements of the MR images, relevant to the distinction of the various subtypes of WMD’s, were identified. In 277 patients with known WMD these elements were analysed, scored according to a protocol and fed into a database. The frequency of occurrence of each MR abnormality was assessed per disease category and thus the pattern of abnormalities characteristic for each disease category emerged. Now the programme can be used in the reversed direction. When fed data about MR abnormalities in a new case, the computer produces a differential diagnosis with MR probability and 95 yOconfidence intervals per diagnosis. Such a programme could be developed for other categories, such as congenital abnormalities, gray matter disorders, spinal pathology etc. It will not compete with the accuracy, flexibility or combining power of an experienced MR reader; the programme, however, could serve the less experienced and be a valuable teaching aid. This programme has also prompted further research into recognizable patterns in rare disorders of which too few cases are present in the database to establish frequency patterns of
abnormalities and useful confidence intervals. In this way we were engaged in the description of patterns in peroxisomal disorders [5] followed by patterns in organic and aminoacidopathies [ 61. This latter category poses extreme difficulties for the identification of patterns. This is the result of the various locations in the subcellular structures of the enzymatic deficit, peroxisomal, mitochondrial or cytoplasmic and the multitude of biochemical pathways included in these metabolic disorders. The organic and aminoacidopathies are therefore very variable in their clinical expression and in the morphological and biochemical abnormalities as expressed in the MR images and, at least in some cases, in MR spectroscopy. We have so far identified live patterns. These patterns result from the various consequences of the enzyme deficit within the organelle, with the disturbance of, for example, the oxidative energy supply, with synthesis of certain proteins, vitamins, or neurotransmitters, or with the action of a toxic product generated due to the lacking enzyme and the production of an exces of organic acids. Undoubtedly more patterns will emerge with better understanding of analogies and differences between the various disorders. The patterns identified until now are: 1. Prevalent afRiction of the arcuate fibers, sparing the cerebral white matter, more general, as in Canavan’s disease [7], or more focal, as in 2-hydroxyglutaric aciduria.
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a
b
C
d
Fig. 16. (a-d) Unilateral encephaloclastic schizencephaly. Note that the clefi on the Tl-eighted SE (a) and Tl-weighted IR (b) images is surrounded by a thick layer of gray matter. This, however is the result of the loss of white matter and severe gliotic retraction in this area. The TS-weighted SE image (c) shows some hyperintense areas in the left frontal lobe, which can be mistaken for myelination. The proton density (d) image makes clear that this is caused by gliosis as an extension of a periventricular leukomalacia.
2. Involvement of the basal ganglia together with bilatera1 temporal arachnoid cysts and fronto-temporal atrophy, as in glutaric aciduria type I and methylmalon acidura.
3. Periventricular white matter affliction, as in phenylketonuria [ 81. white matter disease with calcili4. Periventricular cations, as in some phenylketonuria variants [9].
Fig. 17. MR angiography will be applied on a large scale in the years to come and will replace in neurology and neurosurgery angiography.
nearly all diagnostic
Fig. 18. (a and b) Nutritional deficiencies and subacute intoxications may lead to pecular abnormalities. These images are of a 7-year-old boy with a long lasting diet of only french fries (without mayonnaise) and who was admitted with lowered consciousness, desorientation, changed speech pattern. He was shown to have a severe vitamine B complex deficiency. The Tl-weighted (IR) and T2-weighted SE images at the same level show the abnormalities in the thalamus. Note that the IR image allows more easily localization of the lesions in the thalamus.
a
b
Fig. 19. (a and b) Wernicke’s encephalopathy leads to a specific pattern of involvement of brain structures, very similar to what is seen in Leigh’s disease. The T2-weighted transverse images show the lesions in the basal ganglia, predominantly on the right side, the involvement of the mammilary bodies and the peri-aqueductal gray matter, the latter probably causing the hydrocephalus.
5. Generalized supratentorial edema, together with a toxic edema of the brain stem and posterior fossa, with possible evolution towards atrophy, as in maple syrup urine disease [ lo]. In this group of patients one can expect other anomalies, local atrophy, micro- or macrocephaly, subdural effusions or arachnoid cysts, corpus callosum agenesis and so on. Such an analysis of patterns is also prepared for peroxisomal, lysosomal [ 1 l- 131 and mitochondrial disorders [ 14,151. The given examples show that specificity is strongly dependent on the training and experience of the reader of the images. MR superior to CT It has become evident in the last live years that the yield of MR in a number of diagnostic categories is so much higher than that of other imaging modalities, in particular CT, that MR should be the first choice when an imaging modality is required. In fact, in many of these categories no other imaging modality is requested. Mentioned are here: Normal maturation of the brain (myelination, gyration, corpus callosum formation, iron deposition in basal ganglia) [ 161, congenital anomalies of brain and spinal cord [ 171, acquired and hereditary white matter disorders, toxic encephalopathies, refractary partial epilepsy [ 18-201 sellar and parasellar lesions and neuroendocriene disorders, posthypoxic-ischemic en-
a
b
Fig. 20. (a and b) T2-weighted SE transverse images in a 9-year-old boy with delayed development of speech and language. The medical history reports asphyxia during birth. Neurological examination was normal. MR shows selective involvement of the thalamus (arrows).
cephalopathy in infants older than 3 months, intra- and extra-axial tumours, leptomeningeal afllictions 121,221, postoperative, postradiotherapeutic, postchemotherapeutic conditions of the brain, and all lesions of the spine. In some conditions a special role of MR has emerged, such as the therapy monitoring in multiple sclerosis [23]. Other special applications of MR are also unequalled. MR angiography is rapidly developing as a means of obtaining extra information in certain conditions and will replace much of the diagnostically performed angiography. Quantitative flow measurements in the aqueduct and spinal canal will help to understand CSF dynamics in physiological and pathological conditions. Anisotropically restricted diffusion imaging allows a different view on white matter tracts during progress of myelination and white matter disorders [24,25]. Magnetization transfer imaging, realised by off-frequency irradiation of the investigated structures, extracts information from bound protons, otherwise not visible. These new techniques demand still validation in clinical practice but already have shown their potential. In preterm neonates neurosonography plays an important role as a screening device for intracranial hemorrhagic or leukomalacic conditions. The versatility of the ultrasonographic equipment will guarantee this place for the years to come. MR, however, has proved to be of great value even in this category and is uniquely capable of demonstrating selective neuronal loss in cortical laminar necrosis, Sommer’s sector necrosis, necro-
Fig. 21. (a and b) Series of five TZ-weighted SE and one IR (b), images showing the multitude of lesions seen in a mycoplasm infection. Some of these : lesions are symmetrical, for example in the middle cerebellar peduncle, others are spread through the brain. The IR shol NS the inhomogeneity of the lesions (arrow in b) clearer than the T2-weighted SE.
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Fig. 22. Sagittal Tl-weighted gradient echo image of the cervical spine showing beautifully the herniated disc at the C3-C4 level.
sis of the subiculum, of thalamic nuclei and of the Purkinje cells [ 261. There is still a clear role for CT in analysis of bony structures, in the diagnosis of acute hemorrhagic conditions, in the work up of facial anomalies, in acute traumatology of head and spine, postoperative controls, shunt controls in hydrocephalus, and so on. A series of illustrations demonstrates the diagnostic power of MRI (Figs. l-25). MR spectroscopy (MRS) Though some clinical applications start to emerge, MRS is still very much a research tool. The progress made, however, in the last few years is considerable. Volume-selection is now possible on commercial machines, the required minimal volumen for ‘H spectroscopy has decreased considerably, chemical shift imaging will be a routine procedure in a relatively short time. The claim of positron emission tomographists that PET looks at metabolism and MRS at metabolites more and more proves to be a sophism. First of all in disorders of muscle metabolism, but gradually also in other organs, liver, heart and brain, MRS enables analysis of metabolic chains and the effect of interventions. MRS has the potential to identify the anabolic or catabolic products of a certain metabolite. This comes with the advantage that MRI and MRS can be per-
formed on the same machine, so that no adaptations of the frame of reference are necessary to combine image data with chemical shift images of metabolites. MR spectroscopy is a demanding technique and the interpretation of the results is only possible with consideration of all technical details of both acquisition and postprocessing techniques. For example: In the analysis of the ‘H-spectra of the brain of patients with hepatocerebral syndromes longer echotimes (135 ms or more) do not show the myo-inositol peak, which is visible at shorter echotimes (20 ms or less). This peak shows the most constant abnormality in the spectrum in this kind of intoxication [27,28]. As in MR imaging brain maturation is an important factor in MR spectroscopy. Normal values of 31P and ‘H-MR spectroscopy of all ages with different techniques have to be collected. It is not sufficient to compare the data of a patient with one or two age matched controls, as is often done. The variation in normal individuals is of such a magnitude that normal values have to be acquired from a statistical adequate number of normal individuals per age group, defining the normal value and the standard variation. We performed such a study [29] in normal infants, children and adolescents with regard to ‘H and 31P spectroscopy. The influence of brain maturation on 31P and ‘H spectra was clearly shown, as was the fact that the effects of maturation of the brain are longer noticeable in MRS than in MRI. The ‘H spectra were made with a TE of 270 ms and therefore metabolites with a much shorter T2 are not visible in the spectra. Since ‘H spectroscopy with TEs of 20 ms and less is now feasible, normal values for these TEs have to be obtained. MRS can be partially used in the differentiation between demyelinating and neuronal disorders [ 301. For that purpose 35 patients with a degenerative cerebral disorder, 24 with a demyelinating disorder, 11 with a neuronal disorder, were examined. Four grades of demyelination and 3 grades of cerebral atrophy were graded on basis of MRI criteria. The spectroscopic data were compared with normal values. A statistically significant decrease of the PDE//?-ATP was found with an increasing degree of demyelination. The spectral abnormalities appeared to be synchronous with the abnormalities in the images. With an increasing degree of cerebral atrophy a decreasing NAA/Cr was found. Also this finding was statistically significant. This decrease in NAA/Cr, however, occurred before the MR images showed signs of cerebral atrophy in patients with a neuronal disorder. This last phenomenon was recently also described in patients with the AIDS dementia complex (Fig. 26a-d).
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Fig. 23. (a-d) MR Tl-weighted
SE images of the cervico-thoracic spine, without (a and b) and with contrast (c and d). The cord is swollen is caused by a cyst like structure with rounded upper pole. After contrast there is enhancement of a di stinct nodule within the cyst, with some? linear structures with low signal intensities, probably vessels. Diagnosis, hemangioblastoma, confirmed by histology. Complete recovery after surgery.
ove1 . the whole length and the distension
Conclusion Never before radiologists and clinicians possessed such a powerful diagnostic tool. This tool is at the same time demanding a great investment of its users, especi-
ally in the effort to acquire the knowledge and experience to extract the maximum of the wealth of data offered by both MRI and MRS.
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f
Fig. 24. (a 0 Series of sagittal images of the cervico-thoracic spine, proton density and T2-weighted SE (a and b) where a lesion Mrith s:omelwhat prot jably :r sign l;i, ntensity is first visible on the T2-weighted image (arrow in b). After Gd-DTPA there is clearly enhancement of a lez with cereb lral necrosis at the level of Th2-3. The enhanced area has irregular borders. In the Tl-weighted SE coronal images 01.the lung also :nh ancing lesions are seen, with the same pattern. The diagnosis in this ll-year-old young man was Wegener’s dise :ase.
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