Applied Radiology

Dr. Wirt is a Radiology Resident in the Department of Radiology at Tripler Army Medical Center, Honolulu, HI. Dr. Petermann is a Neuroradiologist at Tripler Army Medical Center, HI; and an Assistant Professor in the Department of Radiology, Uniformed Services University, Bethesda, MD.

Portions of this article were previously presented as a poster presentation at the ASNR annual meeting in San Diego, May 1999; as well as in a presentation, MRS: The Good, The Bad, and The Ugly, at Ski the Sky, Big Sky Radiology Course, Big Sky, MT, February 2002.

Magnetic resonance spectroscopy (MRS) is becoming more frequently used and easier to perform. With a software package addition, an MR instrument can be fully equipped to perform multiple types of MRS. Faster slew rates and gradients provide improved signal-to-noise ratios, even when a smaller voxel sample size is selected. ¹ This article will attempt to simplify the basic MRS concepts in the context of data acquisition and interpretation employed in neuroradiology. The concepts presented here are based on single-voxel MRS with a repetition time (TR) of 1700 msec and an echo time (TE) of 30 msec. Even so, the basic concepts are the same with respect to choline, lactate, lipid, and N-acetyl aspartate. These concepts can be utilized with two-dimensional (2D) or three-dimensional (3D) imaging, using smaller voxel size or variations in voxel size.

MR spectroscopy is a complex field employing the basic principles of nuclear magnetic resonance spectroscopy (NMR) and MRI to obtain clinically relevant information. This article will not attempt to explore the more subtle nuances of MRS nor discuss the numerous qualitative measurements that can be performed. The goal of this article is to allow the general radiologist to feel comfortable with the basic principles of reading MRS and to be able to decide rapidly whether the pattern is abnormal or normal. We will briefly review several types of MRS that radiologists can perform, the three main metabolites, some theory on why MRS changes with various pathologic processes, and how to identify and interpret some main patterns of the spectral graphs.

What is MR spectroscopy?

Rather than displaying MRI proton signals on a gray scale as an image depending on its relative signal strength, MRS displays the quantities as a spectrum. In routine MR imaging, the more edema on a T2 sequence from mobile protons, the brighter the signal on T2. Using MRS, the more metabolite that is present, the taller the peak or greater the area under the peak. Specific metabolites can be located along an x-axis, which is expressed in parts per million (ppm), a dimensionless unit. We can infer that a spectrum of the brain is normal from numerous years of studying such spectra in healthy subjects in whom peak positions and relative intensity ratios have been established (Table 1 and Figure 1). ^2,3

Data acquisition

Once an MR image is obtained as a localizer image, a volume of interest is selected. If a single voxel is to be analyzed, then a single 3D region of interest is selected. Once the single voxel is obtained, the spectrum is collected based on the amount of protons in the voxel. The proton signals are detected and represented as a free induction decay (FID). A Fourier transform is applied to the FID, converting the temporal information into frequency information. The resonant frequency is then plotted versus signal intensity on a spectrum, instead of the typical gray-scale image. If multiple voxels are to be evaluated, then both a region of interest for evaluation and a region of normal brain are selected for comparison (Figure 2). Of the single-voxel techniques, two commonly used acquisition sequences are stimulated echo acquisition mode (STEAM) and point resolved spectroscopy (PRESS). With twice the signal of STEAM, PRESS acquisitions are faster; however, spectral baselines are better with STEAM sequences. Care must be taken when identifying voxels of interest (especially for the normal brain comparisons), since significant regional differences in metabolite distributions can be seen in both gray and white matter (Figure 3). ⁴ Regions to be avoided when selecting voxels include blood, bone, and cysts, since susceptibility artifacts may skew the expected normal molecular distributions. Areas that are difficult to image include the posterior fossa and the spinal cord (both of which encounter problems due to their proximity to bone), as well as tumors containing cystic components, blood, or regions of calcification.

Main metabolites­­The Good, The Bad, and The Ugly

Although there are several metabolites included in the spectrum of single-voxel MRS, we will review the most important in this article.

There are three main players in MRS of the brain: N-acetyl aspartate (NAA), choline (Cho), and the lactate and lipid groups (LL) (Figure 4). An explanation of these three metabolites can bring most physicians up to speed on the basics. Although there are several theories as to why the relative concentrations of each metabolite change, ^2,3,5,6 this introduction will briefly discuss some basic theories behind why each metabolite may change from the normal ratio.

NAA = neuronal health (The Good)

N-acetyl aspartate is seen at 2.02 ppm and is believed to be a marker of neuronal health. Originally, decreases in NAA were considered to be due to neuronal destruction, since it was diminished in cases of multiple sclerosis and following trauma. Since it can be reversible, however, this is probably better described as a marker proportional to the health of the neurons. Higher peaks indicate more normal neuronal presence, while diminished peaks occur in situations in which neural damage or replacement has occurred.

Cho = Tumor marker or cell wall marker (The Bad)

Choline is seen at 3.22 ppm and is present in cell walls of normal brain tissue. As more brain cells are made, one theory suggests the Cho is increased. Active tumor growth will then cause an increase in Cho, since there is above-normal production of cells. Other processes can release or increase Cho besides tumor; multiple sclerosis or acute infarctions will also release Cho, or cause lysis of cell walls, and increase the concentration of Cho. This can be a transient effect, however, while tumors will demonstrate persistent Cho elevation. We call it The Bad, since tumors show an increase in this metabolite.

LL = Destruction and necrosis (The Ugly)

Lactate (lactic acid) is seen as a doublet (two peaks close to one another) at 1.33 ppm and is a by-product of anaerobic metabolism. Lipids resonate at the 0.9 to 1.2 ppm range. Both are released with cell destruction or synthesized in necrosis. Increased LL can be seen in necrotic tumors, and in stroke due to destruction of cells, and in abscess. It can also be seen in lower concentrations in intermediate tumors. Lactate and lipid peaks are generally present in aggressive disease processes.

The three-step approach to spectral analysis

Step 1: The quality assurance phase. Is it an adequate spectrum?

Step 2: Is Hunter's angle normal?

Step 3: Starting from the right side of the graph, count off the location and check quantities of The Good, The Bad, and The Ugly. These are located on the x-axis at 2.02 ppm, 3.22 ppm, and the area from 0.9 to 1.33 ppm.

Quality assurance

Just as a bad image can make interpretation difficult or impossible for diagnosis, a bad MRS may not be interpretable. Substances that are difficult for MRS to image include bone, blood, cysts, and cerebral spinal fluid (CSF). It is difficult to obtain spectra of bone and blood due to immobile protons (bone) and shim difficulties (blood). Both CSF and cysts can contain lactate products and, thus, may lead to inaccurately elevated lactate or lipids as well. When performing voxel measurements, you should stay clear of these substances in all three imaging planes. Since the area sampled is a voxel, it acquires signal from regions above and below the box that has been placed.

Examples of an adequate spectrum include good water suppression; otherwise the water peak on the MRS spectrum is so abundant, it will overshadow the other metabolites. The peak occurs at the far left of the spectrum at 4.7 ppm. (Figure 5). Without suppressing the water signal, it will overwhelm signal from the other metabolites and result in an inadequate spectrum where evaluation of peaks with smaller contributions becomes more difficult.

Hunter's angle

Hunter's angle is a term coined from a neurosurgeon, Hunter Sheldon, at Huntington Medical Research Institutes. Instead of doing complex ratios and analysis of the spectra, he simply used his pocket comb. He placed his comb on the spectrum at approximately a 45š angle and connected several of the peaks. If the angle and peaks roughly corresponded to the 45š angle, the curve was probably normal (Figure 6). If the peaks strayed off the comb's angle, the curve was abnormal (Figure 7). This is a quick, useful method to read MRS and determine normal from abnormal. It is important to remember, however, that this angle was used with STEAM spectra from the brain. This article will not address normal spectra elsewhere in the body.

The Good, The Bad, and The Ugly

We can look at NAA, Cho, and LL in a more simplified pattern (Figure 4). First, the zero point on the curve is located at the far right of the x-axis in spectral analysis. N-acetyl aspartate is a neuronal marker, thus making it a high, plentiful peak on the curve in normal brain tissue. We can call this The Good marker. If the neuronal health is good, this peak will be the highest peak. It is located at 2.02 ppm on the x-axis. Elevations do not occur (except in patients with Canavans disease). Decreased NAA can be due to replacement with other metabolites (ie, tumor cell walls) or due to unhealthy neurons, as in diffuse axonal injury, multiple sclerosis, or infarction. It can be reversible.

Next, we moved left on the spectrum to 3.22 ppm on the x-axis, the location of the Cho peak. Remember, we termed Cho The Bad because excess amounts can indicate cell destruction and release of cell walls, or an increase in cell wall synthesis. Excess Cho is an indicator of tumor. It can also be elevated in early phases of cellular destruction and lysis, as in multiple sclerosis and stroke. These can therefore mimic tumor in their early phases.

Finally, there are the LL peaks located between 0.9 and 1.33 ppm. This is termed The Ugly because it is an extremely dreadful finding. Lactate and lipid peaks occur when necrosis and a sizeable amount of cell death occurs. It will be the highest peak on the spectrum in most high-grade tumors with marked depression of the NAA peak. Another cause of increased LL peaks occurs with cellular destruction such as stroke.

The basics

High-grade tumor: Predominantly The Bad and The Ugly. There is abundant LL and Cho. N-acetyl aspartate is depressed from replacement of neurons with cell wall synthesis and necrosis (Figure 8).

Lower-grade tumor: Predominantly The Bad. There is elevated Cho from tumor cell wall synthesis, but not marked elevation in LL from necrosis. Some NAA depression is present (Figure 9).

Stroke or radiation necrosis: Predominately The Ugly. There are decreased NAA and Cho peaks
with elevation of LL from destruction (Figure 10).

Multiple sclerosis: Loss of The Good. There is loss of NAA peak height, but not much elevation in Cho or LL chronically. Early on, both Cho and LL can be elevated (Figure 11) and can mimic tumor. A follow-up MRS will usually demonstrate change.

Conclusion

These are the basic concepts in reading MRS. You may think of MRS as an additional MR sequence. It may help to focus on a differential diagnosis and can be used in conjunction with other imaging. Though there are many more innuendoes that can be learned along the way, remember to systematically ask the three questions:

1) Is it an adequate spectrum?

2) Is Hunter's angle normal or abnormal?

3) How would The Good, The Bad, and The Ugly be measured? Starting from the right, count off and locate heights at the 2.02 ppm, 3.22 ppm, and 0.9­1.33 ppm areas.

Not enough Good--Trauma or multiple sclerosis.

Too much Bad--Usually tumor.

Too much Ugly--Stroke or radiation necrosis.

Too much Bad and Ugly--High-grade tumor.

MR spectroscopy can help to limit a differential diagnosis. It provides a look at what cellular products may be present in the brain. MR Spectroscopy can be used to answer specific clinical questions, such as differentiating between radiation necrosis and tumor recurrence (Figure 12) or to determine where the most aggressive portion of the tumor is located for biopsy. AR