1	MR Spectroscopy: Can It Narrow Your Differential? Tanmaya C. Shah, MD Rona F. Woldenberg, MD Peter B. Kingsley, Ph.D North Shore University Hospital Manhasset, NY
2	Table of Contents What is MR Spectroscopy? Introduction Principles Technique Metabolites Normal Spectra Clinical Applications Unknown lesion characterization Confirm/exclude suspected clinical and neuroradiologic diagnoses Post surgical follow up Conclusion
3	Introduction Magnetic resonance spectroscopy (MRS) is a noninvasive diagnostic modality that generates a spectrum illustrating quantitative measurements of metabolites within a designated volume of brain parenchyma MRS can be used to classify pathology within the brain by allowing comparison of metabolite concentrations in normal and diseased brain parenchyma Pathologic processes alter the concentration of metabolites in a relatively characteristic manner MRS is most useful when considered in the context of clinical history and additional imaging studies
4	Principles MRS uses the same principles of physics as conventional MR to acquire data During data acquisition, the signal from hydrogen atoms in water is suppressed, allowing the signal from hydrogen atoms in other molecules to be recorded The signal data from these other molecules is processed such that a spectrum with a series of peaks is generated
5	Technique Initially, a scout sequence (e.g. FLAIR, DWI, post-contrast) is performed that allows for optimal visualization of the region of interest A volume of interest box (voxel) is then placed in the area in which metabolite concentrations are to be measured A voxel is also placed on the contralateral side in a corresponding ‘normal’ location to be used as a reference CHESS (chemical shift selective) pulse is used to suppress signal coming from protons in water
6	Technique One of two localization protocols are then employed: STEAM – Stimulated echo acquisition mode Uses three 90-degree pulses to obtain a stimulated echo PRESS – Point resolved spectroscopy Uses one 90-degree pulse and two 180-degree pulses to obtain a spin echo Short and long echo time (TE) sequences are obtained, allowing for visualization of different metabolites: Short and long TE allows for identification of the following metabolites: N-Acetyl aspartate (NAA) Creatine (Cr) Choline (Cho) Lactate (Lac) Short TE allows for identification of the following additional metabolites: Lipids (lip) Glutamine and glutamate (Glx) Myo-inositol (mI)
7	Metabolites
8	Normal Spectra Gray Matter White Matter
9	Normal Spectra Basal Ganglia Cerebellum
10	Clinical Applications When do we utilize MR Spectroscopy? Unknown lesion characterization neoplastic vs. non-neoplastic lymphoma vs. toxoplasmosis in HIV patients Confirm/exclude suspected clinical and neuroradiologic diagnoses demyelinating (MS) hypoxic ischemic encephalopathy congenital disoders (e.g. Zellweger Syndrome, adrenoleukodystrophy) Alzheimer’s Disease Post surgical follow up residual/recurrent tumor vs. radiation necrosis
11	Unknown Lesion Characterization Case 1 Findings: Abnormal low T1W signal lesion and high T2W signal lesion in the medial right temporal lobe. The lesion does not enhance or cause significant mass effect. Is this a low grade tumor?
12	Unknown Lesion Characterization Case 1 MRS Findings Lesion shows normal Cho/Cr ratio, with no significant differences in metabolite ratios. No evidence of a lactate or lipid peak. Impression Benign lesion, probably a hamartoma.
13	Unknown Lesion Characterization Case 2 Findings: Axial T1, post contrast image demonstrates a peripherally enhancing mass involving the corpus callosum. Is this a high grade neoplasm?
14	Unknown Lesion Characterization Case 2 MRS Findings The lesion shows increased choline and decreased NAA, with some lipids and lactate. The comparison shows a much higher Cho/Cr ratio and much less NAA. Impression Tumefactive demyelinating lesion.
15	Unknown Lesion Characterization Case 3 Findings: Images show a ring enhancing lesion in the parietal white matter with surrounding edema. Is this a metastatic lesion?
16	Unknown Lesion Characterization Case 3 MRS Findings The lesion shows a low NAA/Cr ratio, a high Cho/Cr ratio, and a significant lacate signal. NAA is relatively preserved, and Cho/Cr is not excessively high. Impression Active lesion in multiple sclerosis.
17	Unknown Lesion Characterization Case 4 Findings: Images show a ring enhancing lesion in the right thalamus with surrounding edema. Is this lymphoma or toxoplasmosis?
18	Unknown Lesion Characterization Case 4 MRS Findings The spectra from the lesion show a high Cho/Cr ratio, large lipid signal, and lactate (double peak). This suggests lymphoma. Toxoplasmosis is expected to have lower Cho/Cr ratio. Impression Lymphoma.
19	Unknown Lesion Characterization Case 5 Findings: Diffuse lesion in the right frontal lobe demonstrates low T1 signal and high T2 signal with no enhancement or mass effect. Is this a metastatic lesion?
20	Unknown Lesion Characterization Case 5 MRS Findings The lesion spectra have a high Cho/Cr ratio and a low NAA/Cr ratio with some lactate and normal lipid levels. Findings suggest a neoplasm. Impression Astrocytoma.
21	Unknown Lesion Characterization Case 6 Findings: Multiple T2 and FLAIR hyperintense lesions in the white matter and involving the corpus callosum. Several areas of enhancement are also seen. Are these lesions related to active multiple sclerosis or a neoplasm?
22	Unknown Lesion Characterization Case 6 MRS Findings The lesion has an elevated Cho/Cr ratio and a slightly low NAA/Cr ratio with a considerable amount of lactate, consistent with neoplasm. Impression Lymphoma.
23	Unknown Lesion Characterization Case 7 Findings: Enhancing left pontine lesion without mass effect or edema, demonstrating low T1W signal and hyperintense T2W signal. Is this a vascular malformation?
24	Unknown Lesion Characterization Case 7 MRS Findings Compared to the control spectrum, the lesion spectrum has elevated choline, possibly elevated myo-inositol, and no excess lipid. This suggests a low-grade Tumor. Demyelinating disease is also possible. Impression Low-grade neoplasm?
25	Unknown Lesion Characterization Case 8 Findings: There is abnormal enhancement and restricted diffusion in the left frontotemporal region. There is surrounding edema causing mild mass effect on the left lateral ventricle. Is this an infarct or a high grade glioma?
26	Unknown Lesion Characterization Case 8 MRS Findings Compared to the control spectra, the abnormal region demonstrates a substantial reduction in all metabolites, favoring an ischemic process rather than a neoplastic process. Impression Left middle cerebral artery infarct.
27	Unknown Lesion Characterization Case 9 Findings: Multiple bilateral basal ganglia, thalamus, posterior parietal (not shown) lesions demonstrating low T1W signal and high T2W signal. There is subtle enhancement, with mass effect on the left lateral ventricle.
28	Unknown Lesion Characterization Case 9 MRS Findings The basal ganglia spectra appear to have slightly high Cho/Cr ratios, slightly low NAA/Cr ratios, and a large Lactate signal. This is consistent with published spectra of cryptococcus.^5,6 Impression Cryptococcus.
29	Confirmation of Diagnoses Case 10 Findings: T2 and FLAIR images show bilateral periventricular white matter lesions, commonly seen in multiple sclerosis.
30	Confirmation of Diagnoses Case 10 MRS Findings Cho/Cr ratio is elevated and there may be some lactate present, consistent with a demyelinating disease. Impression Multiple sclerosis.
31	Confirmation of Diagnoses Case 11 Findings: Areas of increased T2W and FLAIR signal in the left frontal white matter extending into the internal capsule.
32	Confirmation of Diagnoses Case 11 MRS Findings The control spectrum had a lower NAA/Cr ratio and a higher Cho/Cr than expected for normal white matter. Relative to the control spectrum, the lesion had elevated lipid signal and slightly reduced NAA/Cr ratio. This is consistent with ALD, as well as other diseases with lipid breakdown. Impression Consistent with ALD and other diseases with lipid breakdown.
33	Confirmation of Diagnoses Case 12 Findings: Right frontal parenchymal hemorrhage with surrounding edema. Is there an underlying lesion?
34	Confirmation of Diagnoses Case 12 MRS Findings No definite metabolite signals are detected from the site of the bleed (lactate?). Impression No evidence of an under- lying lesion.
35	Confirmation of Diagnoses Case 13 Findings: Images demonstrate bilateral middle cerebral artery distribution infarcts involving the gray and white matter, as well as the genu and splenium. These findings can be related to a global ischemic event.
36	Confirmation of Diagnoses Case 13 MRS Findings The NAA/Cr ratio and NAA/Cho ratios are very low in areas of abnormal diffusion, and slightly low in control regions. Impression Findings are consistent with significant metabolic damage in areas of abnormal diffusion.
37	Confirmation of Diagnoses Case 14 Findings: Involutional changes and periventricular small vessel white matter ischemic changes. Rule out Alzheimer’s Disease.
38	Confirmation of Diagnoses Case 14 MRS Findings The occipital gray matter voxel is commonly used to diagnose Alzheimer’s disease with TE = 30 ms. This spectrum has normal NAA/Cr and mI/Cr ratios, so this does not appear to be Alzheimer’s disease. Impression Normal NAA/Cr and mI/Cr ratios suggest that this is not Alzheimer’s disease.
39	Confirmation of Diagnoses Case 15 Findings: Bilateral caudate head abnormalities.
40	Confirmation of Diagnoses Case 15 MRS Findings Spectrum shows elevated lipids and elevated Choline, suggesting abnormal lipid metabolism. Impression Findings consistent with abnormal lipid metabolism. Zellweger’s Syndrome is a congenital hereditary disorder of peroxisomal dysfunction.
41	Post Surgical Follow Up Case 16 Findings: There is a ring enhancing lesion with surrounding edema in the site of the prior meningioma. Is this radiation necrosis or recurrent tumor?
42	Post Surgical Follow Up Case 16 MRS Findings The lesion has significant lipid signal and a high Cho/Cr ratio. There are overall reduced levels of metabolites, probably from central necrosis. The high Cho/Cr ratio suggests recurrent tumor rather than radiation necrosis.
43	Post Surgical Follow Up Case 17 Findings: In the region of prior resection, there is a minimally enhancing, low T1W signal and high T2 signal abnormality. Is this lymphoma recurrence?
44	Post Surgical Follow Up Case 17 MRS Findings No lactate or excess lipid is seen in the abnormal spectrum. The Cho/Cr ratio is normal. These findings suggest that the lesion does not represent residual or recurrent lymphoma.
45	Conclusion Magnetic resonance spectroscopy is a useful addition to the diagnostic tools available to the neuroradiologist MRS can be used in a number of clinical applications to confirm clinical and radiographic impressions MRS may be helpful in following post operative patients When a lesion cannot be characterized on conventional imaging, MRS may help narrow the differential by identifying the metabolic composition of a lesion MRS is most useful when utilized in conjunction with clinical history and conventional imaging.
46	References 1. Law M, et al. Differentiating Surgical from Non-Surgical Lesions using Perfusion MR Imaging and Proton MR Spectroscopic Imaging. Technology in Cancer Research and Treatment. December 2004; 3(6):557-565. 2. Brandao, LA. MR Spectroscopy of the Brain. Lippincott Williams & Wilkins. 2004 3. Danielsen ER, Ross B. Magnetic Resonance Spectroscopy Diagnosis of Neurological Diseases. Marcel Dekker, Inc. 1999 4. Chang L, Miller BL, McBride D, et al. Brain lesions in patients with AIDS: H-1 MR spectroscopy. Radiology 1995; 197: 525-531 5. Chang L, Ernst T. MR spectroscopy and diffusion-weighted MR imaging in focal brain lesions in AIDS. Neuroimaging Clin. N. Am. 1997; 7: 409-426.