1H-Magnetic Resonance Spectroscopy (MRS) is a novel advanced imaging technique used as an adjunct to MRI to reveal complementary non-invasive information about the biochemical composition of imaged tissue. Clinical uses in paediatrics include aiding diagnosis of brain tumours, neonatal disorders such as hypoxic-ischaemic encephalopathy, inherited metabolic diseases, traumatic brain injury, demyelinating conditions and infectious brain lesions. MRS has potential to improve diagnosis and treatment monitoring of childhood brain tumours and other CNS diseases, facilitate biopsy and surgical planning, and provide prognostic biomarkers. MRS is employed as a research tool outside the brain in liver disease and disorders of muscle metabolism. The range of clinical uses is likely to increase with growing evidence for added value. Multicentre trials are needed to definitively establish the benefits of MRS in specific clinical scenarios and integrate this promising new technique into routine practice to improve patient care. This article gives a brief overview of MRS and its potential clinical applications, and addresses challenges surrounding translation into practice.
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MRI has been available since the 1980s, providing images with excellent structural detail. 1H-magnetic resonance spectroscopy (MRS) is a novel advanced imaging technique used as an adjunct to MRI to reveal complementary non-invasive information about the biochemical composition of imaged tissue. Clinical uses in paediatrics include aiding diagnosis of brain tumours, neonatal disorders such as hypoxic-ischaemic encephalopathy (HIE), inherited metabolic diseases, traumatic brain injury, demyelinating conditions and infectious brain lesions. MRS is employed as a research tool outside the brain in liver disease and disorders of muscle metabolism.
This article gives a brief overview of MRS and its potential clinical applications, and addresses the challenges surrounding translation into practice.
How does MRS work?
1H-MRS uses signals from hydrogen protons (1H) to determine relative concentrations of tissue metabolites including choline (Cho) (involved in membrane synthesis), N-acetylaspartate (NAA) (a neuronal marker) and mobile lipids (increased in apoptosis and necrosis).1 These are represented as a graphical spectrum with peaks corresponding to metabolite concentrations (figure 1). Interpretation allows clinicians to non-invasively evaluate the biochemical environment of imaged tissue.
MRS is performed following MRI. Acquisition from a small region (single voxel spectroscopy) is relatively simple, adding only 5 minutes to examination time with no additional sedation or anaesthesia. Spectroscopic imaging of larger areas provides detailed information on tissue heterogeneity.
Neurological diseases in which MRS is valuable for clinical decision-making
MRS has predominantly been used clinically in evaluation of the central nervous system (CNS) to deliver information about metabolite levels in brain abnormalities.
Early non-invasive diagnosis of paediatric brain tumours would enable timely initiation of treatment, facilitate surgical planning and inform family discussions at a stressful time. Biopsy could be avoided in lesions not requiring upfront resection. Accurate preoperative diagnosis would inform surgeons of prognostic importance of complete resection and allow early referral for radiotherapy.
MRS can be used in clinical practice to add diagnostic value and inform important management decisions2 (this has been published and is reference 10 in the reference list). Normal brain and different tumour types display characteristic MR spectra,3–5 with variations in metabolite levels reflecting histopathological processes.6 Malignant tumours are characterised by high levels of Cho, lactate and lipids, signifying increased membrane synthesis, apoptosis and necrosis. Low NAA reflects loss of neuronal integrity.4 7 Certain metabolite alterations are specific to tumour type, such as elevated taurine in medulloblastoma3 4 and reduced creatine (Cr) in pilocytic astrocytoma (figure 2).3 Diagnosis of the main paediatric cerebellar tumours (pilocytic astrocytoma, medulloblastoma and ependymoma) is possible using their characteristic MR specta4 7–9 (figure 2), with diagnostic decision support tools incorporating computer-based pattern recognition being accurate in single and multinational settings.4 7–9
MRS has been used clinically to target biopsy in heterogeneous paediatric tumours.10 Applying spectroscopic imaging allows identification of highly malignant regions likely to result in diagnostic yield.
Prognosis of histopathologically similar tumours differs considerably. Novel non-invasive MRS biomarkers facilitate tumour characterisation11 and risk stratification. Some apply across a range of tumour types (mobile lipids predict poor survival12; glutamine and NAA improved prognosis13), whereas others are tumour specific (glutamate signifies poor survival in medulloblastoma14). A multivariate model of survival based on three biomarkers has similar accuracy to histopathological grade.13 Metastatic and localised brain tumours display different metabolite profiles, allowing identification of risk of metastatic relapse.11 MRS has been used clinically to identify unusual high-risk paediatric tumours.10
Early indicators of response and relapse
Morphological changes in tumour size do not always correspond to treatment response or progression. Variations in Cho, mobile lipids and myoinositol (MIns) are potential early non-invasive biomarkers of response15 allowing treatment adaptation as disease evolves.11 Pseudoprogression (treatment-related increase in size simulating relapse or progression) can be identified through comparing MRS profiles at different time points.16
Hypoxia-Ischaemia, inherited metabolic diseases, traumatic brain injury
MRS can be used to assess paediatric neuropathologies and is already a valuable tool in the work-up of an encephalopathic neonate. MRS may provide an indication of the severity of neonatal HIE through measuring the concentration of cerebral lactate in the basal ganglia, reflecting prognosis as persistence signifies poor outcome17 and assessing the therapeutic effect of hypothermia.18 MRS may clarify an uncertain diagnosis and can be very helpful to guide towards subsequent investigations for a metabolic diagnosis in otherwise suspected HIE (e.g. raised brain white matter lactate without classical imaging appearance of HIE in mitochondrial disorders).19 Inherited metabolic disorders demonstrate accumulation of neurotoxic metabolites visible on MRS. Pyruvate and succinate are indicative of pyruvate and succinate dehydrogenase complex deficiencies respectively, whereas elevated NAA suggests Canavan disease.19 MRS can reflect outcome in children with traumatic brain injury through NAA/Cr ratio and lactate.20
MRS aids diagnosis of hereditary leukoencephalopathies and demyelination through measurement of Cho/Cr and NAA/Cr ratios. Elevation of MIns/NAA and Cho/NAA in normal-appearing white matter is an indication for haematopoietic stem cell transplantation in inherited demyelinating disorders.21 MRS can characterise white matter abnormality in evolving multiple sclerosis.22 Recovery of NAA signal losses is a favourable prognostic sign in acute disseminated encephalomyelitis.23
Focal lesions caused by infectious agents
MRS plays a role in diagnosis of focal brain infections. Intracranial ring-enhancing lesions can be confirmed as pyogenic abscesses through presence of succinate, acetate, alanine and leucine.24 Tuberculoma can be differentiated from non-tuberculous lesions, with the former showing lactate and lipid signals and lacking cytosolic amino acids.
Uses outside the CNS
MRS has potential uses outside the CNS, including evaluation of liver disease and disorders of muscle metabolism, but remains a research tool in this area. Motion due to cardiac pulsation, respiration and peristalsis is a major barrier to intra-abdominal MRS.
Implementing MRS into routine clinical practice
Routine implementation of MRS is hampered by lack of agreed quality control measures, acquisition protocols and analysis techniques. MRS is a departure from traditional radiological working, and it is difficult to obtain timely quantitative data in a busy clinical environment. Research is being undertaken to determine the optimal use of MRS to add value in defined clinical scenarios, and to overcome challenges in implementation and interpretation to facilitate incorporation of protocols across multicentre settings.
MRS is an important adjunct to MRI with potential to improve diagnosis and treatment monitoring of childhood brain tumours and other CNS diseases, facilitate biopsy and surgical planning, and provide prognostic biomarkers.10 The range of clinical uses is likely to increase with growing evidence for added value. Multicentre trials are needed to definitively establish the benefits of MRS in specific clinical scenarios and integrate this promising new technique into routine practice to improve patient care.
Contributors KAM conducted a review of the literature and wrote and revised the original manuscript. AP reviewed the literature, and reviewed and revised the manuscript prior to submission. Both authors approved the final manuscript.
Funding National Institute for Health Research (NIHR) grant code 13-0053.
Disclaimer The sponsor had no role in the writing of this report or the decision to submit the article for publication.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.
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