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MP 6.01.24 Magnetic Resonance Spectroscopy

Medical Policy    
Original Policy Date
Last Review Status/Date
Reviewed literature search/12:2012
  Return to Medical Policy Index


Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically. 


Magnetic resonance spectroscopy (MRS) is a noninvasive technique that can be used to measure the concentrations of different chemical components within tissues. The technique is based on the same physical principles as magnetic resonance imaging (MRI) and the detection of energy exchange between external magnetic fields and specific nuclei within atoms.

Magnetic resonance spectroscopy (MRS) is a noninvasive technique that can be used to measure the concentrations of different chemical components within tissues. The technique is based on the same physical principles as magnetic resonance imaging (MRI) and the detection of energy exchange between external magnetic fields and specific nuclei within atoms. With MRI, this energy exchange, measured as a radiofrequency signal, is then translated into the familiar anatomic image by assigning different gray values according to the strength of the emitted signal. The principal difference between MRI and MRS is that in MRI, the emitted radiofrequency is based on the spatial position of nuclei, while MRS detects the chemical composition of the scanned tissue. The information produced by MRS is displayed graphically as a spectrum with peaks consistent with the various chemicals detected. MRS may be performed as an adjunct to MRI. An MRI image is first generated, and then MRS spectra are developed at the site of interest, termed the voxel. While an MRI provides an anatomic image of the brain, MRS provides a functional image related to underlying dynamic physiology. MRS can be performed with existing MRI equipment, modified with additional software and hardware.

MRS has been studied most extensively in a variety of brain pathologies. In the brain, both 1-H (i.e., proton) and 31-P are present in concentrations high enough to detect and thus have been used extensively to study brain chemistry. For example, proton MRS of the healthy brain reveals 5 principal spectra:

  • Arising from N-acetyl groups, especially N-acetylaspartate (NAA)

NAA intensity is thought to be a marker of neuronal integrity and is the most important proton signal in studying central nervous system (CNS) pathology. Decreases in the NAA signal are associated with neuronal loss.

  • Arising from choline-containing compounds (Cho), such as membrane phospholipids (e.g., phosphocholine and glycerophosphocholine). Choline levels increase in acute demyelinating disease. Brain tumors may also have high signals from Cho.
  • Arising from creatine and phosphocreatine

In the brain, creatine is a relatively constant element of cellular energetic metabolism and thus is sometimes used as an internal standard.

  • Arising from lipid
  • Arising from lactate

Normally this spectrum is barely visible, but lactate may increase to detectable levels when anaerobic metabolism is present. Lactate may accumulate in necrotic areas, in inflammatory infiltrates, and in brain tumors.

Different patterns of the above spectra and others, such as myoinositol and glutamate/glutamine, in the healthy and diseased brain are the basis of clinical applications of MRS. The MRS findings characteristically associated with non-necrotic brain tumors include elevated Cho levels and reduced NAA levels. The International Network for Pattern Recognition using Magnetic Resonance (Available online at: has developed a user-friendly computer program for spectral classification and a database of 300 tumor spectra with histologically validated diagnoses to aid radiologists in MRS diagnosis. (1)

All the findings reported in this policy refer to proton MRS, unless otherwise indicated.

One of the limitations of MRS is that it provides the metabolic composition of a given voxel, which may include more than one type of tissue. For some applications, the voxels are relatively large (e.g., greater than 1 cm3), although they may be somewhat smaller using a (3 Tesla) 3T MRI machine versus a 1.5T magnet. The 3T technique creates greater inhomogeneities, however, which require better shimming techniques. (2) There are 2 types of MRS data acquisition: single voxel or simultaneous multivoxel, also called chemical shift imaging. Reliable results are more difficult to obtain from some areas, e.g., close to the brain surface or in children with smaller brains because of the lipid signal from the skull. Some techniques are used to deal with these issues; various MRS techniques continue to be explored as well. A combination of MRS is often used with other MRI techniques, including diffusion-tensor imaging, susceptibility-weighted imaging, etc., and possibly other types of imaging such as positron emission tomography (PET).

Peripheral applications of MRS include the study of myocardial ischemia, peripheral vascular disease, and skeletal muscle. Applications in non-CNS (central nervous system) oncologic evaluation have also been explored. Nomograms for prostate cancer are being developed that incorporate MRI and MRS results. (3)

Multiple software packages for performing proton MRS have received clearance by the U.S. Food and Drug Administration (FDA) through the 510(k) process since 1993.


Magnetic resonance spectroscopy is considered investigational.

Policy Guidelines

CPT code 76390 describes magnetic resonance spectroscopy.

Benefit Application
BlueCard/National Account Issues

State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational, and thus these devices may be assessed only on the basis of their medical necessity.


The policy was created in 2000 and has been updated on a regular basis with literature searches of the MEDLINE database. The most recent search was conducted for the period of October 2011 through October 2012. The findings of the literature searches are summarized below.

Validation of a new imaging technique involves the following steps:

  1. Demonstration of its technical feasibility, including assessment of its reproducibility and precision.
  2. An understanding of normal and abnormal values as studied in different clinical situations. For accurate interpretation of study results, sensitivities, specificities, and positive and negative predictive values compared to a reference standard must be known.
  3. The clinical utility of an imaging study is related to how the results of that study can be used to benefit patient management. The clinical utility of both true-positive and true-negative tests must be assessed. Relevant outcomes of a negative test (i.e., suspected pathology is not present) may be avoidance of more invasive diagnostic tests or avoidance of ineffective therapy. Relevant outcomes of a positive test (i.e., suspected pathology is present) may also include avoidance of a more invasive test plus the institution of specific, effective therapy. Use of the imaging study should result in net health benefit.

The published data indicate that the second and third criteria have not been met for magnetic resonance spectroscopy (MRS). MRS has been investigated in a wide variety of clinical situations; key potential applications are discussed below.

Literature Review

There are a variety of potential indications for MRS, both for cancer and non-cancer conditions. The clinical utility of MRS will be evaluated separately for each of these indications.

Brain Tumors

A TEC Assessment was completed in 2003 evaluating MRS for evaluation of suspected brain tumors. The 2003 TEC Assessment (4) used the following study selection criteria to identify studies for inclusion in the MRS assessment:

  1. Sample sizes of 10 or more subjects;
  2. A method to confirm the MRS diagnosis;
  3. Specified criteria for a positive test; and
  4. Available data to calculate diagnostic performance.

The Assessment identified 7 studies including a total of 271 subjects. MRS would be judged to produce a beneficial effect on a health outcome if MRS correctly determined the presence or absence of a tumor and avoided the need for a brain biopsy. The Assessment concluded that MRS did not meet TEC criteria for evaluation of suspected brain tumors. (4)

One study of 12 children treated with radiation for a brain tumor had a magnetic resonance imaging (MRI) scan suggestive of either progressive/recurrent tumor or delayed cerebral necrosis. (5) MRS identified 5 of 7 recurrent tumors, for a sensitivity of 71%. MRS identified 4 of 5 cases (80%) of delayed necrosis, and a fifth case was considered inconclusive.

Five studies that evaluated a heterogeneous group of patients, some with known prior tumor, some with unknown new masses, showed variable diagnostic test characteristics for MRS with sensitivities ranging from 79% to 100% and specificity ranging from 74% to 100%. (6-11) The positive predictive value ranged from 92% to 100%, while the negative predictive value ranged from 60% to 100%. The wide range reported for diagnostic performance in these studies may reflect heterogeneous groups of patients, differences in MRS protocols, or both.

One study evaluated 51 patients with intracranial cystic lesions. (11) MRS properly assigned the correct diagnosis in 47 of 51 patients (92%). However, MRS interpretation was based on investigator judgment, rather than on formal criteria.

The 2003 TEC Assessment concluded that the overall body of evidence did not provide strong and consistent evidence regarding the diagnostic test characteristics or clinical utility of MRS for any condition. Studies of diagnostic performance often included a heterogeneous mix of patients who had clinically important differences and did not clearly delineate how MRS information would be used to guide patient management. Furthermore, differences in MRS technique and methods of analysis across studies made it difficult to synthesize findings from different studies.

A systematic literature review on MRS for the characterization of brain tumors was performed in 2006. This review evaluated whether MRS could differentiate malignant from non-malignant lesions; high-grade tumors from low-grade tumors; and metastatic from primary brain tumors. The review concluded that the evidence on MRS for characterizing brain tumors is promising but that additional high-quality studies are needed. (12) Many of the articles reviewed were flawed, in some cases because of research design and in other cases because key information needed to evaluate the study was not reported (e.g., how many days elapsed between the imaging test and the biopsy, which served as the reference standard).

Other research has attempted to determine whether MRS can differentiate the type of brain tumor. In 2012, Vicente and colleagues reported on a multi-center study to evaluate the ability of single voxel, proton MRS to differentiate 78 histologically confirmed pediatric brain tumors (29 medulloblastomas, 11 ependymomas, and 38 pilocytic astrocytomas). (13) Significant metabolic differences in tumor types were identified by MRS when results from short and long echo times were combined, suggesting that MRS may provide non-invasive diagnostic information.

In 2012, Wilson et al. evaluated MRS as a prognostic tool. This study reported on single voxel, proton MRS using short echo times to predict survival of patients with pediatric brain tumors in 115 patients followed for a median of 35 months. (14) Metabolic changes were identified that predicted survival. Poor survival was associated with lipids and scyllo-inositol while glutamine and N-acetyl aspartate were associated with improved survival (p<0.05).

Studies on the use of MRS to categorize newly diagnosed brain tumors (15); to distinguish between tumors and abscesses or other infectious processes (16); or to diagnose mitochondrial diseases (17) identify the MRS patterns associated with each type of lesion but, once again, do not include the necessary validation study or they report MRS findings that overlap across the categories of interest. Many are also retrospective. (16, 18) Preliminary studies done in Asia with a 3T MRI machine for detecting tumor versus radiation injury reported diagnostic quality MRS studies in 26/28 (93%) cases, and the sensitivity and specificity for those 26 patients based on cutoffs identified in the study were 94.1% and 100%, respectively. (15); see also (19). Validation studies using the same cutoffs in larger samples are needed. (15)

A 2009 review on MRS in radiation injury concludes the following:

MR spectroscopy is presently one of the noninvasive radiologic methods used to distinguish recurrent tumor and radiation injury in patients previously treated with radiation for neoplasm. Still, despite a considerable volume of research in the field, no consensus exists in the community regarding ratio calculations, the accuracy of MR spectroscopy to identify radiation necrosis, and the accuracy of MR spectroscopy in differentiating radiation necrosis from tumor recurrence or the true value of the method in clinical decision making. (20); for another review, see (21).

In a 2011 study, Amin and colleagues compared MRS to single-photon emission computed tomography (SPECT) in the identification of residual or recurrent glioma versus radiation necrosis in 24 patients treated with surgery and radiotherapy. (22) MRS and SPECT results differed in 9 cases of recurrence and were more accurate with SPECT. Specificity and positive predictive value were 100% in both MRS and SPECT; however, sensitivity was 61.1% versus 88.8% and negative predictive value was 46.2% versus 75%, respectively. The use of a single voxel rather than multiple voxels is noted as a limitation in interpreting the MRS results in this study.

Conclusions. Although a number of studies have examined the use of MRS to differentiate between brain tumor recurrence and radiation necrosis, the cumulative evidence remains weak. The studies tend to have small sample sizes (23, 24); they provide incomplete histopathologic data to serve as the reference standard (25); they find that combined imaging modalities, such as MRS and perfusion MRI or diffusion-weighted MRI, outperform MRS by itself (19, 26); or they identify the patterns of interest and the cutoff values for making a diagnosis without providing validation studies. (18, 27) In some cases, a mixed reference standard is used, with histopathologic findings for lesions that are excised, undergo biopsy, or are reviewed at autopsy and longer follow-up for patients not undergoing surgery. (18, 19) Although having a mixed reference standard is not optimal, it may be the only feasible option in patients with brain tumors, some of which are located in parts of the brain not amenable to surgery. Some studies report mostly on primary brain tumors, (15, 19) while others focus mostly on metastases of cancers located in other parts of the body. (23, 25)


Research continues on using MRS to identify dementia, especially in its early stages. A community-based study was conducted to evaluate whether MRS could distinguish between patients with normal cognition (Group 1), dementia (Group 2), or mild cognitive impairment (MCI; Group 3) in a population with a low Mini-Mental State Examination (MMSE) score. (28) From an initial population of 215 with low MMSE scores, MRS results were obtained for 56 patients. Comparing MRS to clinical diagnoses, the results were mixed for MRS, with statistically significant differences in metabolic patterns between patients with dementia (Group 2) and patients without dementia (Group 1 and Group 3) but not between patients with MCI and those with normal cognition (Group 1 vs. Group 3). In a 2012 study, Shiino and colleagues compared proton MRS in 99 patients with Alzheimer's disease (AD), 31 patients with subcortical ischemic vascular dementia (SIVD) and 45 elderly controls. (29) Differences in metabolic patterns were seen in both AD and SVID patients. Especially notable were increases in myoinositol concentration in the hippocampus identified in AD but not in SIVD (0.95 area under the receiver operating characteristic (ROC) curve).

Breast Cancer

MRS is being investigated to improve the specificity of MRI of the breast, which has a high false-positive rate. Bartella et al. conducted a preliminary study using MRS to evaluate suspicious lesions 1 cm or larger identified on MRI. (30) They found that the addition of MRS increased the specificity of MRI in the specific population examined to 88% (23/26) and could have prevented unnecessary biopsies; the sensitivity was 100% (31/31). As the authors note, these findings need to be confirmed in larger studies and with a more diverse set of lesions. In particular, their sample only included one ductal carcinoma in situ (DCIS), and other studies have suggested that the choline peak they used to indicate a positive MRS result may be less likely to occur with DCIS.

Liver Disease

MRS has been evaluated as a noninvasive alternative to liver biopsy in the diagnosis of hepatic steatosis. It has been compared to other noninvasive imaging procedures such as computed tomography (CT), dual-gradient echo magnetic resonance imaging (DGE-MRI), and ultrasonography (US); liver biopsy was the reference standard and a 3T MRI machine was used. In a prospective study of 161 consecutive potential living liver donors, DGE-MRI was reported to be the most accurate test for diagnosing hepatic steatosis. While DGE-MRI and MRS were similar for hepatic steatosis 5% or greater, DGE-MRI outperformed MRS for hepatic steatosis 30% or greater (especially regarding specificity) and on quantitative estimates. (31); see also (32).

Prostate Cancer

The utility of MRS has also been investigated for identifying whether prostate cancer is confined to the organ, which has implications for prognosis and treatment. Wang et al. found that the addition of MRI findings, both endorectal MRI and MRS, improved the accuracy of the staging nomograms traditionally used to predict the likelihood of organ-confined prostate cancer. (33) Although the study was not ideally designed to assess the incremental value of MRS over MRI alone, it found that the area under the ROC curve was larger when MRS was included, but the difference was not statistically significant.

The results of the American College of Radiology Imaging Network (ACRIN) study 6659 were published in April 2009. (34) This prospective, multicenter study compared the use of MRI with and without MRS to identify the extent of prostate cancer by sextant prior to prostatectomy in 134 patients. The results from centralized histopathologic evaluation of prostate specimens served as the reference standard; MRI and MRS images were independently reviewed by 8 readers. With complete data on 110 patients, no difference was found in the area under the ROC curve for MRI alone versus MRI and MRS combined. That is, the use of MRS provided no incremental value in identifying the extent of prostate cancer.

In a meta-analysis of 7 studies (of 140 screened) on using MRS to diagnose prostate cancer, the pooled weighted sensitivity was 0.82 (95% confidence interval [CI]: 0.73–0.89); specificity, 0.68 (95% CI: 0.58–0.76); and the area under the curve, 83.40. (35) All of these results are based on a cutoff for identifying “definitive” tumor of 0.85 for the ratio of (choline plus creatine) to citrate.

A single-institution randomized, controlled trial (RCT) published in 2010 compared conducting a second randomly selected biopsy (group A) to a biopsy selected partly based on MRS and dynamic contrast-enhanced (DCE) MRI results (group B). (36) The participants were selected from 215 consecutive men with an elevated prostate-specific-antigen (PSA) (between 4 and 10 ng/mL), an initial negative biopsy result, and a negative digital rectal examination; 180 patients participated in the study. Cancer was detected in 24.4% of group A patients and 45.5% of group B participants. Fifty patients from group A with 2 negative biopsy results agreed to undergo biopsy a third time using MRS and DCE MRI results; 26 more cancers were found. Overall, 61.6% of the cancers detected had Gleason scores 7 (4+3) or more. The cancers detected after using MRS and dynamic contrast-enhanced MRI imaging also lined up with the suspicious areas detected on imaging. The sensitivity and specificity of MRS were 92.3% and 88.2%, respectively; adding dynamic, contrast-enhanced MRI increased the sensitivity to 92.6%, and the specificity to 88.8%. Limitations of the study include that it was conducted at a single center, analysis was confined to the peripheral zone of the prostate gland, and more samples were drawn from group B patients than from group A patients (12.17 vs. 10 cores, respectively). Furthermore, given the concerns about potential overtreatment among patients with early stage prostate cancer, the benefits of detecting these additional cancers need to be evaluated by examining clinical outcomes for these patients. Similar issues arise in Policy 7.01.121 on saturation biopsy of the prostate.

In a similar report from this institution by these authors, 150 patients with a negative prostate biopsy, despite PSA elevations, were randomized to MRS or MRS plus DCE-MRI to locate prostate cancer foci for a second targeted biopsy. (37); see also (38). The addition of DCE-MRI to MRS yielded increased sensitivity and specificity over MRS alone (93.7% and 90.7% versus 82.8% and 91.8%, respectively). Pedrona and colleagues also reported on the combined use of MRS and DCE-MRI for prostate cancer in 106 patients in a prospective cohort study. (39) The authors reported combined MRS and DCE-MRI results yielded unacceptably low positive predictive value of 19%. Negative predictive value was 91%. Sensitivity was 71% and specificity was 48%. The authors indicated the combined MRS and DCE-MRI may be useful in avoiding biopsy since the negative predictive value was 91%; however, further study is needed.

Gauging Treatment Response

The possibility of using MRS to track treatment response and failure has been explored. A small (n=16), preliminary study of tamoxifen treatment for recurrent gliomas found MRS patterns differed between responders and nonresponders. (40) Serial MRS demonstrated that metabolic spectra stabilized after initiation of therapy among responders and then changed in advance of clinical or radiologic treatment failure. In other words, MRS might help predict imminent treatment failure. However, there are relatively few studies with small sample sizes assessing this possible use of MRS. In addition, a number of other types of imaging are being evaluated for the same use, including dynamic, contrast-enhanced MRI, diffusion-weighted MRI, and 18-fluorodeoxyglucose position emission tomography (FDG-PET). Additional studies are needed, including studies comparing modalities or evaluating multimodalities. (41, 42)

Other Indications

MRS has also been evaluated for other uses, such as tracking disease changes among patients with multiple sclerosis (MS), (43) assessing carotid plaque morphology, (44) as biomarkers of traumatic brain injury (45) predicting long-term neurodevelopmental outcome after neonatal encephalopathy, (46); but see also (47) and other applications in children. (48, 49) Additional evidence on these applications is needed.

Ongoing Clinical Trials

A search of online site in November 2012 identified many studies using MRS as a research tool. Two active studies on the utility of MRS include the use of MRS to detect cervical cancer (NCT01060033) and for guidance on glioma treatment choice (NCT01263821).

Physician Specialty Society and Academic Medical Center Input

In 2008, in response to requests, input was received from 3 physician specialty societies and 1 academic medical center while this policy was under review. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. The input received from these reviewers disagreed with the conclusions in the policy statement. In particular, information provided was in support of MRS in differentiating radiation necrosis from recurrent tumor and in the differential diagnosis of certain CNS tumors from non-tumors.


Magnetic resonance spectroscopy (MRS) is a noninvasive technique that can be used to measure the concentrations of different chemical components within tissues. The available studies do not provide strong and consistent evidence regarding the diagnostic test characteristics of MRS. Studies do not clearly delineate how MRS information would be used to guide patient management. Thus, it is not possible to determine whether MRS provides relevant clinical information that will safely influence diagnostic thinking and therapeutic choice. The scientific evidence at this time does not permit conclusions concerning the net effect of this technology on health outcomes. Therefore, the use of MRS is considered investigational.

Practice Guidelines and Position Statements

The National Comprehensive Cancer Network’s clinical practice guidelines on central nervous system tumors identifies MRS, along with MR perfusion or brain PET, as a modality that can be considered to rule out radiation necrosis, as compared to recurrence of brain tumors. (50) The authors also state that MRS may be helpful in grading tumors or assessing response and that the most abnormal area on MRS would be the best target for biopsy. The limitations include tumors near vessels, air spaces, or bone; the extra time required in an MRI machine; and the limitations occurring with any MRI, such as the exclusion of patients with implantable devices. The guidelines on prostate cancer mention MRS as a possible element of “more aggressive workup for local recurrence (e.g., repeat biopsy, MR spectroscopy, endorectal MRI),” which is one possible element of salvage therapy for patients after radical prostatectomy with rising PSA or positive digital rectal examination after radical prostatectomy with a negative biopsy and studies negative for metastases. (51) The guideline on breast cancer does not mention MRS.

The American College of Radiology updated its practice guideline on MRS of the CNS in 2008. (52) Most of the guideline is devoted to the actual performance of MRS, but it also lists 22 possible indications for MRS when MRI or CT are inadequate for answering specific clinical questions.

Medicare National Coverage

In January 2004, Medicare issued a decision memorandum for MRS for brain tumors that reaffirmed its national noncoverage determination. (53) After reviewing updated literature, a technology assessment it commissioned from the Agency for Healthcare Research and Quality, and the BCBSA TEC Assessment, Medicare found that there was not adequate evidence to conclude that MRS is reasonable and necessary for the diagnosis of brain tumors.


  1. Sibtain NA, Howe FA, Saunders DE. The clinical value of proton magnetic resonance spectroscopy in adult brain tumours. Clin Radiol 2007; 62(2):109-19.
  2. Sood S, Gupta A, Tsiouris AJ. Advanced magnetic resonance techniques in neuroimaging: diffusion, spectroscopy, and perfusion. Semin Roentgenol 2010; 45(2):137-46.
  3. Hricak H, Choyke PL, Eberhardt SC et al. Imaging prostate cancer: a multidisciplinary perspective. Radiology 2007; 243(1):28-53.
  4. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Magnetic resonance spectroscopy for evaluation of suspected brain tumor. TEC Assessments 2003; Volume 18, Tab 1.
  5. Taylor JS, Langston JW, Reddick WE et al. Clinical value of proton magnetic resonance spectroscopy for differentiating recurrent or residual brain tumor from delayed cerebral necrosis. Int J Radiat Oncol Biol Phys 1996; 36(5):1251-61.
  6. Rand SD, Prost R, Haughton V et al. Accuracy of single-voxel proton MR spectroscopy in distinguishing neoplastic from nonneoplastic brain lesions. AJNR Am J Neuroradiol 1997; 18(9):1695-704.
  7. Adamson AJ, Rand SD, Prost RW et al. Focal brain lesions: effect of single-voxel proton MR spectroscopic findings on treatment decisions. Radiology 1998; 209(1):73-8.
  8. Kimura T, Sako K, Gotoh T et al. In vivo single-voxel proton MR spectroscopy in brain lesions with ring-like enhancement. NMR Biomed 2001; 14(6):339-49.
  9. Lin A, Bluml S, Mamelak AN. Efficacy of proton magnetic resonance spectroscopy in clinical decision making for patients with suspected malignant brain tumors. J Neurooncol 1999; 45(1):69-81.
  10. Wilken B, Dechent P, Herms J et al. Quantitative proton magnetic resonance spectroscopy of focal brain lesions. Pediatr Neurol 2000; 23(1):22-31.
  11. Shukla-Dave A, Gupta RK, Roy R et al. Prospective evaluation of in vivo proton MR spectroscopy in differentiation of similar appearing intracranial cystic lesions. Magn Reson Imaging 2001; 19(1):103-10.
  12. Hollingworth W, Medina LS, Lenkinski RE et al. A systematic literature review of magnetic resonance spectroscopy for the characterization of brain tumors. AJNR Am J Neuroradiol 2006; 27(7):1404-11.
  13. Vicente J, Fuster-Garcia E, Tortajada S et al. Accurate classification of childhood brain tumours by in vivo(1)H MRS - A multi-centre study. Eur J Cancer 2012 [Epub ahead of print].
  14. Wilson M, Cummins CL, Macpherson L et al. Magnetic resonance spectroscopy metabolite profiles predict survival in paediatric brain tumours. Eur J Cancer 2012 [Epub ahead of print].
  15. Zeng QS, Li CF, Zhang K et al. Multivoxel 3D proton MR spectroscopy in the distinction of recurrent glioma from radiation injury. J Neurooncol 2007; 84(1):63-9.
  16. Garg M, Gupta RK, Husain M et al. Brain abscesses: etiologic categorization with in vivo proton MR spectroscopy. Radiology 2004; 230(2):519-27.
  17. Bianchi MC, Tosetti M, Battini R et al. Proton MR spectroscopy of mitochondrial diseases: analysis of brain metabolic abnormalities and their possible diagnostic relevance. AJNR Am J Neuroradiol 2003; 24(10):1958-66.
  18. Weybright P, Sundgren PC, Maly P et al. Differentiation between brain tumor recurrence and radiation injury using MR spectroscopy. AJR Am J Roentgenol 2005; 185(6):1471-6.
  19. Zeng QS, Li CF, Liu H et al. Distinction between recurrent glioma and radiation injury using magnetic resonance spectroscopy in combination with diffusion-weighted imaging. Int J Radiat Oncol Biol Phys 2007; 68(1):151-8.
  20. Sundgren PC. MR spectroscopy in radiation injury. AJNR Am J Neuroradiol 2009; 30(8):1469-76.
  21. Martinez-Bisbal MC, Celda B. Proton magnetic resonance spectroscopy imaging in the study of human brain cancer. Q J Nucl Med Mol Imaging 2009; 53(6):618-30.
  22. Amin A, Moustafa H, Ahmed E et al. Glioma residual or recurrence versus radiation necrosis: accuracy of pentavalent technetium-99m-dimercaptosuccinic acid [Tc-99m (V) DMSA] brain SPECT compared to proton magnetic resonance spectroscopy ((1)H-MRS): initial results. J Neurooncol 2012; 106(3):579-87.
  23. Kimura T, Sako K, Tohyama Y et al. Diagnosis and treatment of progressive space-occupying radiation necrosis following stereotactic radiosurgery for brain metastasis: value of proton magnetic resonance spectroscopy. Acta Neurochir (Wien) 2003; 145(7):557-64; discussion 64.
  24. Schlemmer HP, Bachert P, Henze M et al. Differentiation of radiation necrosis from tumor progression using proton magnetic resonance spectroscopy. Neuroradiology 2002; 44(3):216-22.
  25. Chernov MF, Hayashi M, Izawa M et al. Multivoxel proton MRS for differentiation of radiation-induced necrosis and tumor recurrence after gamma knife radiosurgery for brain metastases. Brain Tumor Pathol 2006; 23(1):19-27.
  26. Truong MT, St Clair EG, Donahue BR et al. Results of surgical resection for progression of brain metastases previously treated by gamma knife radiosurgery. Neurosurgery 2006; 59(1):86-97; discussion 86-97.
  27. Rock JP, Hearshen D, Scarpace L et al. Correlations between magnetic resonance spectroscopy and image-guided histopathology, with special attention to radiation necrosis. Neurosurgery 2002; 51(4):912-9; discussion 19-20.
  28. Garcia Santos JM, Gavrila D, Antunez C et al. Magnetic resonance spectroscopy performance for detection of dementia, Alzheimer's disease and mild cognitive impairment in a community-based survey. Dement Geriatr Cogn Disord 2008; 26(1):15-25.
  29. Shiino A, Watanabe T, Shirakashi Y et al. The profile of hippocampal metabolites differs between Alzheimer's disease and subcortical ischemic vascular dementia, as measured by proton magnetic resonance spectroscopy. J Cereb Blood Flow Metab 2012; 32(5):805-15.
  30. Bartella L, Morris EA, Dershaw DD et al. Proton MR spectroscopy with choline peak as malignancy marker improves positive predictive value for breast cancer diagnosis: preliminary study. Radiology 2006; 239(3):686-92.
  31. Lee SS, Park SH, Kim HJ et al. Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. J Hepatol 2010; 52(4):579-85.
  32. Taouli B, Ehman RL, Reeder SB. Advanced MRI methods for assessment of chronic liver disease. AJR Am J Roentgenol 2009; 193(1):14-27.
  33. Wang L, Hricak H, Kattan MW et al. Prediction of organ-confined prostate cancer: incremental value of MR imaging and MR spectroscopic imaging to staging nomograms. Radiology 2006; 238(2):597-603.
  34. Weinreb JC, Blume JD, Coakley FV et al. Prostate cancer: sextant localization at MR imaging and MR spectroscopic imaging before prostatectomy--results of ACRIN prospective multi-institutional clinicopathologic study. Radiology 2009; 251(1):122-33.
  35. Wang P, Guo YM, Liu M et al. A meta-analysis of the accuracy of prostate cancer studies which use magnetic resonance spectroscopy as a diagnostic tool. Korean J Radiol 2008; 9(5):432-8.
  36. Sciarra A, Panebianco V, Ciccariello M et al. Value of magnetic resonance spectroscopy imaging and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy. Clin Cancer Res 2010; 16(6):1875-83.
  37. Panebianco V, Sciarra A, Ciccariello M et al. Role of magnetic resonance spectroscopic imaging ([(1)H]MRSI) and dynamic contrast-enhanced MRI (DCE-MRI) in identifying prostate cancer foci in patients with negative biopsy and high levels of prostate-specific antigen (PSA). Radiol Med 2010; 115(8):1314-29.
  38. Panebianco V, Sciarra A, Lisi D et al. Prostate cancer: 1HMRS-DCEMR at 3T versus [(18)F]choline PET/CT in the detection of local prostate cancer recurrence in men with biochemical progression after radical retropubic prostatectomy (RRP). Eur J Radiol 2012; 81(4):700-8.
  39. Perdona S, Di Lorenzo G, Autorino R et al. Combined magnetic resonance spectroscopy and dynamic contrast-enhanced imaging for prostate cancer detection. Urol Oncol 2011 [Epub ahead of print].
  40. Sankar T, Caramanos Z, Assina R et al. Prospective serial proton MR spectroscopic assessment of response to tamoxifen for recurrent malignant glioma. J Neurooncol 2008; 90(1):63-76.
  41. Dhermain FG, Hau P, Lanfermann H et al. Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol 2010; 9(9):906-20.
  42. Harry VN, Semple SI, Parkin DE et al. Use of new imaging techniques to predict tumour response to therapy. Lancet Oncol 2010; 11(1):92-102.
  43. Bellmann-Strobl J, Stiepani H, Wuerfel J et al. MR spectroscopy (MRS) and magnetisation transfer imaging (MTI), lesion load and clinical scores in early relapsing remitting multiple sclerosis: a combined cross-sectional and longitudinal study. Eur Radiol 2009; 19(8):2066-74.
  44. Hermus L, Tielliu IF, Wallis de Vries BM et al. Imaging the vulnerable carotid artery plaque. Acta Chir Belg 2010; 110(2):159-64.
  45. Kou Z, Wu Z, Tong KA et al. The role of advanced MR imaging findings as biomarkers of traumatic brain injury. J Head Trauma Rehabil 2010; 25(4):267-82.
  46. Thayyil S, Chandrasekaran M, Taylor A et al. Cerebral magnetic resonance biomarkers in neonatal encephalopathy: a meta-analysis. Pediatrics 2010; 125(2):e382-95.
  47. Wilkinson D. MRI and withdrawal of life support from newborn infants with hypoxic-ischemic encephalopathy. Pediatrics 2010; 126(2):e451-8.
  48. Rossi A, Gandolfo C, Morana G et al. New MR sequences (diffusion, perfusion, spectroscopy) in brain tumours. Pediatr Radiol 2010; 40(6):999-1009.
  49. Yuh EL, Barkovich AJ, Gupta N. Imaging of ependymomas: MRI and CT. Childs Nerv Syst 2009; 25(10):1203-13.
  50. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Central Nervous System Cancers; v2:2012. Available online at: Last accessed November 2012.
  51. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Prostate Cancer. V.3.2012. Available online at: Last accessed November 2012.
  52. American College of Radiology (ACR) and American Society of Neuroradiology (ASNR). ACR-ASNR practice guideline for the performance and interpretation of magnetic resonance spectroscopy of the central nervous system. Available online at: Last accessed November 2012.
  53. National Coverage Determination for Magnetic Resonance Spectroscopy. Decision Memo for Magnetic Resonance Spectroscopy for Brain Tumors (CAG-00141N). Centers for Medicare and Medicaid Services. 2004. Available online at: Last accessed November 2012.





CPT 76390 Magnetic resonance spectroscopy
ICD-9 Procedure    
ICD-9 Diagnosis   Investigational for relevant diagnoses
ICD-10-CM (effective 10/1/14)   Investigational for all diagnoses
  C50.11- C50.929 Malignant neoplasm of breast code range
  C61 Malignant neoplasm of prostate
  C71.0 – C71.9 Malignant neoplasm of brain code range
  F01.50-F03 Dementia code range
  G35 Multiple sclerosis
  K70.0 – K77 Diseases of liver code range
ICD-10-PCS (effective 10/1/14)   ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this imaging but the codes for MRI might be used.
  B030Y0Z, B030YZZ, B030ZZZ Imaging, central nervous system, magnetic resonance imaging, brain, codes specific to whether or not contrast is used
  BF35Y0Z, BF35YZZ, BF35ZZZ Imaging, hepatobiliary system and pancreas, magnetic resonance imaging, liver, codes specific to whether or not contrast is used
  BH30Y0Z, BH30YZZ, BH30ZZZ, BH31Y0Z, BH31YZZ, BH31ZZZ, BH32Y0Z, BH32YZZ, BH32ZZZ Imaging, skin, subcutaneous tissue and breast, magnetic resonance imaging, codes specific to bilateral or right or left breast, and whether or not contrast is used
  BV33Y0Z, BV33YZZ, BV33ZZZ Imaging, male reproductive system, magnetic resonance imaging, prostate, codes specific to whether or not contrast is used
Type of Service Radiology
Place of Service Outpatient


Magnetic Resonance Spectroscopy
Spectroscopy, Magnetic Resonance

Policy History

Date Action Reason
04/30/00 Add to Radiology section New policy
04/29/03 Replace policy Information updated with TEC Assessment; policy statement unchanged
04/16/04 Replace policy Medicare policy added; policy statement unchanged
07/15/04 Replace policy Literature review update for the period of May 2003 through June 2004; references added; policy statement unchanged
12/14/05 Replace policy Literature update through October 2005; policy statement unchanged
12/12/06 Replace policy Policy updated with literature review through October 2006; policy statement unchanged. Reference numbers 18-23 added
05/08/08 Replace policy Policy updated with literature review through April 2008; reference numbers 1, 2, and 25-35 added; clinical input reviewed. Policy statement unchanged
07/09/09 Replace policy Policy updated with literature search; references 22 and 25 deleted; references 34-39 added; references renumbered. No change to policy statements
11/11/10 Replace policy Policy updated with literature search; Rationale extensively revised. References 2, 23, 24, 28, 31, 32, 34-42, 44 added; reference 43 updated. No change to policy statement
12/08/11 Replace policy Policy updated with literature search. References 25, 30-31 added; references 46-48 updated. No change to policy statement
12/13/12 Replace Policy Policy updated with literature search. References 13-14, 29 and 38 added. No change to policy statement