Pathological Conditions

Infarction

One of the common questions encountered is differentiation of an infarct from a tumor. Some tumors such as low-grade astrocytomas and anaplastic astrocytomas may have an appearance similar to an infarct and can be erroneously diagnosed as infarcts under these conditions. Correct diagnosis can be aided by obtaining spectroscopy. Another scenario is development of an infarct around the time of resection of a tumor. Apparently, this is not uncommon; some authorities believe the incidence of this event to be as high as 10%. In these situations, positive identification of an infarct can usually be accomplished with diffusion-weighted imaging. Spectroscopy can also be helpful.

Neurons are very sensitive to ischemia. As soon as delivery of oxygen and nutrients ceases, anaerobic glycolysis takes over. As a result, lactate is produced and is easily detectable by spectroscopy by its characteristic doublet appearance at 1.3 ppm.

Fig. 1. Normal spectrum. chol, choline; Cr, creatine; NAA, N-acetyl aspartate.

Soon after this (in about 30-60 min), the NAA peak begins to diminish (6). Loss of neurons is irreversible, and as a result, the NAA peak remains low while the lactate peak gradually diminishes only to increase again in the subacute and chronic stages because of migration of macrophages that are naturally rich in lactate. Figure 2 demonstrates an acute infarct. Figure 3 demonstrates a tumor that was erroneously diagnosed as an infarct initially. MRS revealed the true nature of the lesion.

Brain Tumors

According to some authors, spectroscopy is abnormal in every case of brain tumor. This is probably too optimistic, as every practitioner of MRS will testify. It is safe to state that spectroscopy is abnormal in the great majority of brain tumors.

Tumors of the brain are either extraaxial or intraaxial and in each case, they replace the normal neuronal population. As expected, there is a reduction in NAA. Some tumors show spectra in which there is a peak at 2.0 ppm. This is probably because they contain material structurally akin to NAA. NAA is strictly confined to adult neurons.

Tumors also cause a large peak of choline, apparently caused by rapid turnover of cell membranes with accumulation of material used in the synthesis of membranes, or material generated by degradation of cell membranes. A high peak of choline is seen in both intraaxial and extraaxial tumors. In the intraaxial tumors, it can be seen in both tumors of glial origin and others, for example, metastases and lymphomas. A high choline peak, however, is not confined to neoplastic conditions and can be seen in other diseases, for example in

Fig. 2. (A) Right basal ganglionic acute infarct. (B) The corresponding single-voxel spectroscopy shows decreased N-acetyl aspartate (NAA) and a prominent lactate (LAC) peak. A TE of 40 ms was used.

demyelinating plaques of tumefactive multiple sclerosis (see Demyelinating Disease following). Among gliomas, the choline peak may be higher in anaplas-tic astrocytomas than glioblastomas. One important observation made by many investigators is that in tumors, the site with the highest choline peak does not necessarily correspond to the site of enhancement; this site may reside outside the enhancing portion of the lesion. This fact is potentially significant in choosing an appropriate site for biopsy.

Lactate peak and mobile lipid peaks are seen in more malignant tumors and in those with necrosis. The cystic spaces within a tumor are high in lactate. One note of caution is that even in more benign lesions, after a therapeutic intervention (radiation and/or surgery) a lactate peak may appear (7-10).

Different portions of tumor may have different spectroscopic signatures. Tumors tend to be inhomogeneous, and a complete spectroscopic picture cannot be obtained with single-voxel spectroscopy, hence the need to develop 2D and 3D spectroscopy methods that are more complicated. In many centers, these are fairly routine now, and with 3D volume spectroscopy, the entire brain can be sampled in less than 20 min.

Figures 4 and 5 demonstrate spectroscopy of a glioma and a meningioma, respectively.

The spectra produced by metastases, lymphomas, and malignant gliomas may be quite similar. It is noteworthy that spectra obtained in peritumoral regions in glioma show increased choline. This increased choline is not seen in peritumoral regions of metastases (11). Castillo et al. (12) report that myoinositol

Fig. 3. Medulloblastoma of left cerebellum. (A) A left cerebellar lesion with sharply defined margins and a quadrilateral shape, suggesting an infarct. Note mild mass effect in the fourth ventricle. (B) Corresponding spectra from a multivoxel study with a TE of 140 ms shows increased choline (chol), a depressed N-acetyl aspartate (NAA) peak, and a small lactate (LAC) peak. The spectra are strongly in favor of a neoplastic process. Compare with surrounding normal voxels, for example, voxel #9 in the bottom right.

Fig. 3. Medulloblastoma of left cerebellum. (A) A left cerebellar lesion with sharply defined margins and a quadrilateral shape, suggesting an infarct. Note mild mass effect in the fourth ventricle. (B) Corresponding spectra from a multivoxel study with a TE of 140 ms shows increased choline (chol), a depressed N-acetyl aspartate (NAA) peak, and a small lactate (LAC) peak. The spectra are strongly in favor of a neoplastic process. Compare with surrounding normal voxels, for example, voxel #9 in the bottom right.

Fig. 4. (A) A large hemispheric tumor with mass effect. (B) MR spectroscopy shows elevated choline, decreased NAA, and a lactate peak.
Fig. 5. Spectroscopy of a meningioma. (A) A posterior fossa meningioma. (B) Spectroscopy demonstrates increased choline (Cho), and decreased N-acetyl aspartate (NAA). An alanine (Ala) peak is an inconsistent finding in meningiomas.

is present in all tumors arising from the central nervous system and is absent in metastases. With anaplastic astrocytomas and glioblastomas, there is a trend toward lower myoinositol levels compared with those of low-grade astrocy-tomas (12). In addition, within the glial family of tumors, it is not currently possible to differentiate between different cell lines, for example, between oligo-dendrogliomas and astrocytomas.

Radiation Necrosis

Perhaps the purest form of brain radiation necrosis can be seen in patients with head and neck cancer whose brain is injured because of its proximity to the primary site of tumor. Such brain lesions may be seen in temporal and frontal lobes. Radiation necrosis produces a rather flat spectrum because of reduction in the amount of NAA and choline. Lactate may be seen, however. Several investigators have shown that in severe radiation necrosis there may be an elevated choline peak. This choline peak makes differentiation of recurrent tumor from radiation necrosis difficult (13).

Abscesses and Other Infections

Necrotic tissue seen in some tumors has a different spectroscopic signature compared with that seen in pyogenic infections. Several investigators have shown this, both in vitro and in vivo. Bacteria producing pyogenic infections possess enzymes that are capable of breaking proteins into amino acids. Identification of cytosolic amino acids (leucine, isoleucine, and valine) by spectroscopy is essential in appreciating the pyogenic nature of a lesion. These amino acids produce a peak at 0.9 ppm (14). This peak, upright when spectroscopy is obtained with a TE of about 40 ms, becomes inverted with a TE of 140 ms. Several authors have shown a similar appearance with cysticercosis. Besides these amino acids, lactate and acetate may be seen. Figure 6 shows spectroscopy of a pyogenic abscess.

Tuberculous infections lack such amino acids. Lipids and lactate may be seen. Herpes simplex encephalitis causes significant reduction of NAA and a lactate peak. With AIDS encephalitis, there is an irreversible loss of NAA (15).

Demyelinating Disease

In active lesions (those with enhancement), there is a mild elevation of choline, and a lactate/lipid peak may be seen (16,17). A highly elevated, towering choline peak may be seen in some case of fulminant demyelination (5). Because of similarities with brain tumors, MRS may not be able to differentiate the two. Decreased NAA is a bad sign that (along with T1 black holes, and low magnetization transfer ratio) may signal loss of neurons and poor prognosis.

Epilepsy

The role of spectroscopy in evaluation of patients with medically refractory seizure is controversial. Currently, scalp electroencephalography and tailored MR can be used effectively to localize lesions and help with lateralization. In a certain percentage of patients, these strategies may fail or may provide discordant

Fig. 6. (A) MRS of a well-defined lesion with a thin rim of contrast enhancement and surrounding edema. Spectroscopy was accomplished with TEs of 40 and 140 ms. (B) Note reversal of the peak belonging to cytosolic amino acids (Aminoa) at 0.9 ppm when TE is switched from 40 to 140 ms. This lesion was a nocardia brain abscess. Lac, lactate.

TE=40 TE=140

Fig. 6. (A) MRS of a well-defined lesion with a thin rim of contrast enhancement and surrounding edema. Spectroscopy was accomplished with TEs of 40 and 140 ms. (B) Note reversal of the peak belonging to cytosolic amino acids (Aminoa) at 0.9 ppm when TE is switched from 40 to 140 ms. This lesion was a nocardia brain abscess. Lac, lactate.

results. In these patients PET imaging, SPECT imaging, and MRS can be used (18). Several studies have demonstrated a reduction in the choline-to-NAA ratio in the temporal lobes responsible for seizure. Achten et al. (19) have found the NAA/chol+Cr ratio to be even more helpful than PET in lateralization. Capiz-

zano et al. (20) report that in patients with mesial temporal lobe epilepsy, in the ipsilateral hippocampus the absolute NAA was 18.5% lower compared with that in the contralateral side. Asserting that metabolic changes can be found in other parts of the temporal lobe and brain, these authors found that lateralization could improve if whole temporal lobe data, rather than hippocampal data, were employed (20). Also, a lactate peak may be seen in the immediate postic-tal period in the responsible temporal lobe and in lesser amounts in the contralateral temporal lobe. Whether these observations will lead to universal employment of MRS in the evaluation of patients with refractory seizures remains to be seen.

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