Clinical mr spectroscopy techniques and applications pdf

The recent improvements in spatial resolution have been impressive and the technique is slowly becoming more quantitative. Given the flexibility of clinical magnetic resonance techniques, particularly magnetic resonance imaging, it is likely that MRI will be the diagnostic tool of choice in a wider range of diseases, such as multiple sclerosis, stroke, neurodegenerative conditions, sports injuries and in staging malignancies.

Since proton magnetic resonance spectroscopy packages have become a routine addition to many MRI systems, it is feasible to select the MRI sequences of most value in highlighting anatomical and pathological abnormalities and to incorporate specifically selected MRS sequences to emphasize biochemical differences. Improvements in technical methodologies are central to further developments. For example, use of internal coils, such as implantable or endoscopic coils, will enable small regions of tissue to be studied in considerable detail, which may otherwise be inaccessible to measurement.

A deeper seeded component of the mass with a rim of enhancement reaches the wall of the ipsilateral ventricle. More subtle T2-signal abnormalities are seen in the adjacent temporal and parietal gyri in the ipsilateral thalamus, in the corpus callosum, and left frontal lobe. The spectral grid gives an overview of the dramatic heterogeneous metabolic changes. In the deeper seeded enhancing component, Cho is only moderately elevated, while the dominant peak is lipid, a sign of necrosis.

Note the marked elevation of Cho in multiple spectra of the surrounding tissue despite the subtle hyperintensity on T2-weighted MR images. Note elevated Cho signal also in the left frontal lobe where a small nodule of enhancement is seen on post-Gd T1weighted MR images. Normal spectra are seen in the voxels adjacent to the tumor, immediately outside of the T2hyperintensity.

Also in this case metabolic changes are localized within the area of T2signal abnormality. A normal spectrum from the contralateral temporal lobe 1 is shown for comparison. In the deeper seeded enhancing component of the mass 3 there is a strong signal from mobile lipids, a sign of necrosis, in association with depletion of Cr and NAA; the Cho signal is also relatively weak. A susceptibility artifact at the craniotomy site is hyperintense on the Cho and Cr maps arrows.

Bright signal around the brain on the Lip and NAA maps arises from residual lipid signals from the scalps. Response to therapy in lymphoma. The pretreatment study shows a right parietal white matter mass containing elevated Cho and lipid, and absent Cr and NAA. There is a progressive reduction of Cho and lipid signals from the lesion during treatment, accompanied by restoration of normal brain metabolites Cr and NAA. At 33 months after diagnosis, Cho and lipid signals within the mass returned to normal levels.

Reproduced with permission from Bizzi et al. Supratentorial locations are rare. These tumors are composed of densely packed cells with hyperchromatic nuclei and scant cytoplasm. Focal areas of hemorrhage and necrosis are frequently found. The presence of leptomeningeal metastases is often associated with PNET, therefore staging with MRI of the spine must be performed before surgery. Histologically, they are very well circumscribed and separated from the brain.

In , Wang et al. More recently, it has been shown that an abnormally elevated taurine signal 3. The medulloblastoma shows low levels of NAA, as well as elevated levels of Cho, lactate, and lipids, and peaks assigned to taurine Tau and guanadinoacetate Gua. Pilocytic astrocytomas typically have low levels of Cr, as well as elevated lactate in this example.

As in adults, high-grade astrocytomas show increased Cho compared to low grade, while NAA is absent in both examples.

Reproduced with permission from Panigrahy et al. Despite these challenges, 1H-MRS will continue to be an important tool for physicians working to improve brain tumor diagnosis, prognosis, and therapy. A molecular genetic model of astrocytoma histopathology. Brain Pathol ; 7: — References [8] Hengartner MO. Biochemistry of apoptosis.

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J Neurosurg ; 74— Intraaxial brain masses: MR imaging-based diagnostic strategy — initial experience. Preoperative proton MR spectroscopic imaging of brain tumors: correlation with histopathologic analysis of resection specimens. MR-spectroscopy guided target delineation for high-grade gliomas. Correlations between magnetic resonance spectroscopy and image-guided histopathology, with special attention to radiation necrosis.

Neurosurgery ; —9; discussion — Can J Neurol Sci ; 13— Proton MR spectroscopy of pediatric cerebellar tumors. Untreated pediatric primitive neuroectodermal tumor in vivo: quantitation of taurine with MR spectroscopy. Prognostic value of proton MR spectroscopy of cerebral hemisphere tumors in children. Neuroradiology ; —5. Introduction: MR spectroscopy in stroke A stroke is the rapidly developing loss of brain function due to vascular failure to supply adequate blood nutrients to the brain.

Stroke can be due to ischemia lack of blood supply caused by thrombosis or embolism, or due to a hemorrhage vasculature rupture. Increasingly, imaging is also being used to guide therapeutic interventions and monitor their success.

Traditionally, X-ray computed tomography has been the imaging modality of choice, primarily because of its speed and widespread availability. MRI has been used increasingly because of its excellent soft tissue contrast, high sensitivity and multimodal capabilities e.

While proton MRS studies performed in the early s showed promise for its diagnostic value in acute stroke, MRS has had relatively little clinical impact since then. Several reasons may explain this lack of clinical use. Nevertheless, it is important to be aware of the spectroscopic correlates of acute and chronic infarction, and on occasion MRS may be helpful, particularly when trying to distinguish ischemic from non-ischemic lesions.

Most proton MRS studies of human stroke have focused on the signals from N-acetyl aspartate NAA and lactate, as potential surrogate markers of neuronal integrity and ischemia, respectively. However, there are also often changes in the other metabolite signals, particularly in the chronic stages of brain infarction. Lactate is seen to increase and NAA decrease steadily over a time period of 12 h. Choline and creatine signals are relatively unchanged.

Reproduced with permission from [79]. Such a large and severe metabolic abnormality has a very poor prognosis; the patient died 3 days later. For instance, NAA reductions were found to be greater in the core of the ischemic region compared to the periphery in the study by Higuchi et al. The origin of this is uncertain, but it has been suggested that this may be due to the presence of more than one pool of NAA, or 2. In infarcted brain e.

In addition to loss of NAA, this case also exhibited elevated lactate and choline signals. Acute ischemia injury causes phosphocreatine to be converted to creatine, but no net change in the total creatine, so it is tempting to use the creatine as a reference signal in the spectrum. However, more recent studies have suggested that creatine may change in both acute and chronic infarction,[14] so it is probably unwise to assume that creatine levels are always normal in human stroke.

Cho The choline signal Cho, 3. Choline has been observed to either be increased or decreased in chronic human stroke. Lactate In normal human brain, lactate 1. When the brain becomes hypoxic or ischemic, the lack of oxygen results in an inability for glucose to be metabolized through the normal tricarboxylic acid TCA cycle. Hence, hypoxia or ischemia causes an elevation in brain lactate.

It should be noted that ischemia and infarction are not the only causes of increased brain lactate. Reported CBF thresholds may vary depending on the animal model used, gray or white matter, the type of anesthesia, the type and duration of ischemia, arterial oxygenation and hematocrit, and the method used to measure CBF.

For instance, in both animal models of ischemia and in human stroke, elevated lactate in peri-infarct 93 Chapter 6: MRS in stroke and HIE regions with near-normal NAA levels has been reported. If the duration and severity of ischemia is short enough e. Lactate was highest in the acute stage, and it was also higher in the most extensive ischemic strokes, whereas it is generally barely detectable by the chronic stage 3 weeks. Many of these early MRS studies of human stroke used single-voxel localization methods.

However, single-voxel techniques do not provide information regarding the spatial distribution and extent of metabolic abnormalities, and require that the location of the ischemic or infarcted region be already known or visible on MRI studies. To address these issues, it is possible to use MR spectroscopic imaging MRSI methods for the study of cerebral ischemia, either in one[19,37,38] or two spatial dimensions,[17,39] or using multi-slice 2D MRSI.

Conventional T2-weighted MR images were normal, while proton MRSI at 24 h after symptom onset revealed elevated lactate throughout the right MCA territory, with the highest concentration in the basal ganglia Figure 6.

Since there were no signs of infarction at this stage, the patient was treated with hypervolemic hypertensive hemodilution therapy and improved clinically. Follow-up imaging performed one week later Figure 6. This case shows that, as expected, during the earliest stages of stroke, the main spectroscopic abnormality is an increase in lactate.

Elevated lactate in the absence of any other sign of infarction suggests that ischemic tissue at risk of infarction i. Potentially, if emergent MRSI is available in acute stroke patients, this type of information could be useful in making treatment decisions regarding thrombolysis or other interventions.

Minimal changes are visible in the conventional T2weighted MRI; however, spectroscopic images show an elevation of lactate through much of the right middle cerebral artery territory, indicating ischemia. NAA is relatively preserved in the right hemisphere, with mild reduction only compared to the left.

B Follow-up imaging performed one week later shows development of infarction in the right basal ganglia T2 hyperintensity, absence of NAA. Lactate is present only in the region of infarction.

High Cho is seen in the peri-infarct white matter. As an example, Figure 6. MR spectroscopy in hypoxic—ischemic encephalopathy Hypoxic—ischemic encephalopathy HIE results from prolonged oxygen deprivation, and may be caused by 2. HIE is most commonly encountered in perinatal asphyxia in neonates, where hypoxia is the primary insult, and will be the focus of discussion in this section.

In addition to perinatal asphyxia, hypoxic—ischemic injury can occur in children and adults. In children, this often results from drowning, hanging, choking, and non-accidental trauma particularly in young children. In adults, cardiac arrest or cerebrovascular disease with secondary hypoxemia is the more frequent cause,[43,44] as discussed in the previous section.

In term infants the estimated frequency is 0. Unresponsive year-old male. Adapted, with permission, from [42]. In order to measure severity of HIE and to monitor clinical progress, several grading systems have been devised, of which the most widely used is the Sarnat score. Management of HIE is mainly supportive care and prevention of secondary CNS insults such as due to seizures and metabolic derangement. MR imaging is an important part of evaluation of these infants, and may provide important information Chapter 6: MRS in stroke and HIE about the site, extent, severity, and etiology of cerebral injury, as well as prognostic factors.

T1- or T2-weighted MRI generally lacks sensitivity in the acute phase, as the visible MRI abnormalities may not become apparent until several days after onset of injury at which point neuroprotective therapy is probably too late. Proton MRS changes during brain development from term birth onwards have been discussed in Chapter 4, so this section largely focuses on the term and preterm neonate.

Normal phosphorus spectra from neonatal 1 week , infant 1 year and adult brain 36 years. Note the high levels of PME in the neonatal brain, which decrease in intensity relative to the other metabolites as the brain matures; absolute quantitation indicates this is mainly due to increases in other metabolites ATP, PCr, etc. Adapted, with permission, from [57]. The less well developed white matter region has lower levels of all metabolites.

Preterm gray matter shows very high myo-inositol mI and low NAA; thalamus has high levels of choline Cho and creatine Cr. Spectra from preterm infants at term are virtually identical to those from term infants.

Reproduced with permission from [61]. Preterm at term Fullterm 4. Detailed studies in regional 31P spectra in term and preterm neonates as a function of gestational age have not been performed, however.

Detailed metabolic changes as a function of gestational age are available in the literature. In particular, all basal ganglia metabolite levels except lactate are high, presumably because of the higher cellular density of the more mature tissue Figure 6.

Higher lactate signals in the CSF than in the brain are also found. One issue of debate is the detectability of lactate in normal term or preterm neonates.

The ability to detect and quantify a lactate signal depends on many factors, in particular signal-to-noise SNR ratio, pulse sequence, anatomical region of interest, and analysis software used.

Representative short echo time single voxel spectra from neonates of 25, 35, and 49 weeks gestational age. Of note is the decrease of mI and increase in NAA with age. A small lactate peak is also clearly visible in the younger neonates. Normative curves showing evolution of NAA, lactate Lac and glutamine Glu with gestational age from 20 to weeks are shown. Reproduced with permission from [63]. Although there have been several studies reporting no detectable MRS lactate signal in normal term neonatal brain,[60,64,65] other studies have reported a lactate signal.

Note that the thalami have the most mature spectra, with lowest choline and highest NAA peaks, and the frontal white matter has the least mature spectra. Reproduced with permission from [80]. Immature myelination may be another factor that improves shimming. ATP is also typically decreased. Changes of this nature e. This has been studied in some detail, both in human neonates as well as appropriate animal models. Other reported spectral changes include increased Glx and lipid,[63,72] most likely due to release of free triglycerides as membrane breakdown occurs, and loss of Cr, probably due to decreased cellularity.

Reproduced with permission from [81]. Figure 6. In the HIE spectrum, lactate Lac is conspicuously high and NAA is low, an alanine Ala methyl doublet is just visible, and two prominent features, probably mainly due to glutamine Gln , are present at 2. Note also the prominent peak from propan-1,2-diol PD resulting from anti-seizure medications administered to the HIE infant.

It is important not to confuse this doublet peak 1. A Control. Reproduced with permission from [74]. This compound readily crosses the blood—brain barrier and has a characteristic pattern on 1H MRS of a doublet centered at 1.

The spectrum during hypoxia was recorded at the end of the insult, and demonstrates a high lactate peak 8. Upon resuscitation, there is an initial recovery to a normal metabolic pattern 2 h , followed by an increase in lactate and decrease in NAA, corresponding to secondary energy failure at 24—48 h later. Adapted with permission from [71]. Using the same model as in Figure 6.

Blood Lac measurements were 1. Reproduced with permission from [71]. A—C were performed at day 1 16 h , D—F were performed at 4 days 84 h , and G—I were performed at 8 days h.

A Axial T1-weighted image at age 16 h is normal. C Proton MR spectroscopy from the right thalamus at age 16 h shows minimal elevation of lactate Lac , but is otherwise normal. D Axial T1-weighted image at 84 h shows that the normal hyperintensity in the posterior limb of the internal capsule is no longer seen. Abnormal hyperintensity is seen in the ventrolateral thalami and posterior putamina. Note that the NAA and choline peaks have continued to decrease in size compared with the creatine peak.

Reproduced with permission from [52]. Furthermore, follow-up imaging studies suggested that acute MRI and DWI underestimated the topological extent of injury. Gullapalli, D. Lin N2 - In vivo magnetic resonance spectrosopy MRS is increasingly being used in the clinical setting, particularly for neurological disorders.

AB - In vivo magnetic resonance spectrosopy MRS is increasingly being used in the clinical setting, particularly for neurological disorders. Clinical MR Spectroscopy: Techniques and applications.

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