European Journal of Cardiovascular Medicine

Cerebral ring-enhancing lesions (RELs) represent one of the most challenging radiological entities in neuroimaging. These lesions exhibit a characteristic “ring-like” pattern of contrast enhancement — a central area of necrosis or cystic degeneration surrounded by a peripheral rim of enhancement on contrast-enhanced MRI. However, this radiologic appearance is non-specific, as it can be seen in a wide range of pathologies, including infectious, neoplastic, inflammatory, and vascular causes such as tuberculoma, neurocysticercosis, abscess, metastasis, glioma, or subacute infarction (1–3).

Differentiating these etiologies is essential, as the management, prognosis, and follow-up strategies vary significantly. For instance, tuberculomas require long-term antitubercular therapy, whereas neurocysticercosis necessitates antiparasitic and corticosteroid therapy. Abscesses demand antibiotic coverage or surgical drainage, while neoplastic lesions may need surgical resection, radiotherapy, or chemotherapy. Thus, early and accurate differentiation is crucial to reduce morbidity and avoid inappropriate treatment (2,4).

Conventional Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are the primary diagnostic tools. Although MRI provides excellent anatomic detail and superior soft-tissue contrast, it primarily offers morphological rather than metabolic information. As a result, different lesions can appear similar on standard T1- and T2-weighted sequences, leading to diagnostic overlap. This is particularly true for tuberculoma and neurocysticercosis, which often present as multiple small ring lesions at the gray-white matter junction and may appear indistinguishable on conventional MRI (1,3,5).

In recent years, advanced MRI techniques such as Diffusion Weighted Imaging (DWI), Perfusion Weighted Imaging (PWI), and Proton Magnetic Resonance Spectroscopy (¹H-MRS) have enhanced the diagnostic capability of MRI in differentiating ring-enhancing lesions (4,6,7). DWI assesses water diffusivity and is helpful in identifying pus or necrosis, while PWI evaluates lesion vascularity and cellularity. Among these, Magnetic Resonance Spectroscopy (MRS) provides unique biochemical information by measuring the relative concentrations of brain metabolites such as choline (Cho), creatine (Cr), N-acetylaspartate (NAA), lipids, and lactate, which reflect underlying cellular metabolism (5,8,9).

MRS offers significant diagnostic value because each pathological process exhibits a distinctive metabolic signature. NAA, a neuronal marker, is reduced in neuronal loss or dysfunction. Choline is a marker of membrane turnover and cell proliferation, often elevated in neoplasms and demyelination. Creatine remains relatively stable and serves as an internal reference. Lactate and lipids indicate anaerobic metabolism, necrosis, or infection (7,8). Amino acids and succinate are typically associated with bacterial or parasitic infections (6,9,10).

By analyzing these metabolites, MRS can distinguish between infectious, inflammatory, and neoplastic lesions. For instance, tuberculomas show prominent lipid peaks due to the mycobacterial cell wall, whereas neurocysticercosis (NCC) demonstrates elevated lactate and succinate without significant lipid peaks (11–13). Primary or metastatic brain tumors are characterized by markedly increased choline and reduced NAA, while abscesses exhibit amino acid and inverted lactate peaks (10,14–16).

In resource-limited and tuberculosis-endemic regions such as India, the challenge of distinguishing tuberculoma from NCC persists, despite the routine availability of MRI. Misdiagnosis can result in either unwarranted antitubercular therapy or delayed antiparasitic treatment, both of which can significantly impact clinical outcomes (12,15). Therefore, the incorporation of MRS into diagnostic evaluation provides a non-invasive, radiation-free, and highly specific metabolic assessment that complements conventional imaging (8,17,18).

Rationale of the Study

Despite widespread MRI accessibility, the integration of MRS into diagnostic workflows remains inconsistent due to variability in acquisition protocols, interpretation standards, and clinician familiarity. Given its potential to refine differential diagnosis, MRS warrants systematic evaluation in tertiary care settings in India, where infectious etiologies predominate among ring-enhancing lesions (1,11,14,19,20).

Aim

To evaluate the role of proton Magnetic Resonance Spectroscopy (¹H-MRS) in the differential diagnosis of cerebral ring-enhancing lesions, correlating specific metabolic patterns with underlying pathologies.

Objectives

• To analyze MRS metabolite patterns (Cho, Cr, NAA, lipids, lactate, amino acids, succinate) in patients with cerebral ring-enhancing lesions.
• To compare choline/creatine ratios and identify diagnostic trends distinguishing infectious from neoplastic etiologies.
• To differentiate tuberculoma and neurocysticercosis based on their distinctive MRS spectral profiles.
• To assess the clinical implications of MRS in treatment planning and prognosis

Study design and setting

A prospective observational study was performed at Government Erode Medical College and Hospital, Perundurai, Erode, Tamil Nadu, India, between February 2020 and April 2021 after Institutional Ethics Committee approval and written informed consent from participants (or guardians for minors).

Sample size and participants

From 64 patients screened with ring-enhancing lesions on contrast-enhanced MRI, 50 patients (31 males, 19 females; age 3–82 years) met inclusion criteria and underwent MRS. Exclusion criteria included claustrophobia, incompatible metallic implants (including pacemakers), chronic kidney disease (precluding contrast administration), pregnancy, and known psychiatric illness impairing consent.

MRI and MRS acquisition

All imaging was performed on a Siemens Symphony 1.5 T scanner using standard brain protocols: axial T1- and T2-weighted sequences, FLAIR, coronal T2, sagittal T1, post-contrast T1 in axial/coronal/sagittal planes, DWI, and T2* gradient echo. Single-voxel 1H-MRS was acquired with TE = 20 ms and TE = 144 ms. The voxel was placed centrally to include maximal lesion tissue, margins, and adjacent normal brain where feasible; spectroscopy was avoided when voxel contamination by bone/artifact was likely or the lesion was too small for reliable voxel placement.

Metabolite analysis

Spectra were analyzed visually and quantitatively using the scanner software. Peaks recorded included choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), lactate (Lac), lipids, succinate, and amino acids. Choline/creatine (Cho/Cr) ratios were calculated. Typical spectral patterns used for diagnostic inference were:

• Tuberculoma: prominent lipid peak; Cho/Cr often 1–2.
• Neurocysticercosis (NCC): lactate and succinate peaks; insignificant lipid peak (depending on stage).
• Pyogenic abscess: amino acid resonances and lactate peak.
• Neoplasm (primary/metastatic): elevated choline and decreased NAA; Cho/Cr >2 often suggests high-grade tumor.

Statistical analysis

Data were analyzed using R (v3.6.0). Categorical variables are reported as counts and percentages. Descriptive statistics were used for metabolite distribution and lesion characteristics. No inferential tests were performed due to the observational design and sample size.

Lesion Characteristics:

Among the 50 patients evaluated, the distribution of ring-enhancing lesions across anatomical and morphometric parameters is summarized in Table 1.
Lesions located in the midline region were least frequent (4%), whereas those affecting a single hemisphere (either right or left) were more common. With regard to lesion number, multiple lesions were predominant, with 2–4 lesions observed in 44% of patients and >4 lesions in 24%, while solitary lesions were detected in 32% of cases.When analyzed by size, the majority of lesions measured less than 2 cm (60%), followed by 2–4 cm in 28%, and only 12% exceeded 4 cm.This distribution highlights that small, multiple, subcortical ring-enhancing lesions are typical imaging patterns among the studied population, consistent with infectious etiologies commonly encountered in endemic regions (Table 1).

Lesion Type Distribution:

The diagnostic classification based on MRS spectral patterns and clinical correlation is presented in Table 2.Tuberculoma emerged as the most prevalent pathology, accounting for 36% of all cases, followed by neurocysticercosis (NCC) at 22%, and pyogenic abscesses at 10%.Neoplastic lesions collectively comprised a smaller proportion of the sample — primary brain tumors (6%) and metastatic lesions (8%) — whereas tumefactive demyelination was rare, noted in only one patient (2%).These findings indicate that infectious granulomatous lesions (tuberculoma and NCC combined) constituted more than half (58%) of all cases, reaffirming the predominance of infectious causes of ring enhancement in the Indian population (Table 2).

Spectroscopy Findings:

The metabolite distribution patterns derived from MRS analysis are detailed in Table 3.
The choline peak was the most frequently elevated metabolite, observed in 66% of patients, indicating increased membrane turnover or cellular proliferation.Lipid peaks, representing necrotic or mycobacterial content, were detected in 50% of patients, most commonly in cases of tuberculoma.Lactate peaks, which reflect anaerobic metabolism, were present in 48% of patients, predominantly among those diagnosed with neurocysticercosis or abscesses.A reduction in N-acetyl aspartate (NAA), suggestive of neuronal loss or dysfunction, was observed in 12% of patients.Moreover, an elevated choline-to-creatine (Cho/Cr) ratio greater than 2 was noted in 16% of cases, correlating strongly with primary and metastatic neoplasms.

Collectively, these metabolite signatures facilitated differentiation between the major diagnostic categories.For example, tuberculomas typically exhibited high lipid and moderate choline peaks (Cho/Cr = 1–2), neurocysticercosis showed lactate and succinate peaks with minimal lipid expression, and neoplastic lesions demonstrated high choline with reduced NAA and Cho/Cr > 2.Thus, the integration of MRS findings significantly enhanced the diagnostic accuracy of MRI in evaluating ring-enhancing lesions (Table 3)

Table 1: Study summary

Table 2: Lesion type distribution

Table 3: Key metabolite findings

Demographics and clinical presentation

Fifty patients were included (mean age 36.8 ± 21.6 years). Males numbered 31 (62%) and females 19 (38%). Seizures were the most common presenting symptom (42/50; 84%). Other symptoms included headache (11/50; 22%), fever (9/50; 18%), vomiting (3/50; 6%), ataxia (4/50; 8%), and motor weakness (1/50; 2%).

Lesion characteristics

Laterality: right-sided lesions in 13 (26%), left-sided in 20 (40%), bilateral in 15 (30%), and midline in 2 (4%). Lesion multiplicity: single lesions in 16 (32%), 2–4 lesions in 22 (44%), and >4 lesions in 12 (24%). Lesion size distribution: <2 cm in 30 (60%), 2–4 cm in 14 (28%), and >4 cm in 6 (12%).

Final clinical/MRS-probable diagnoses

The lesion-type distribution (n=50) was:

• Tuberculoma: 18 (36%)
• Neurocysticercosis: 11 (22%)
• Abscess: 5 (10%)
• Metastasis: 4 (8%)
• Primary brain tumor: 3 (6%)
• Tumefactive demyelination: 1 (2%)
• Other (radiation necrosis, granuloma not otherwise specified, etc.): 8 (16%)

Spectroscopy findings

Key MRS observations:

• High choline peak was identified in 33 patients (66%); this was particularly marked in primary tumors and many metastases.
• Lipid peaks were prominent in 25 patients (50%), most consistently observed in tuberculomas.
• Elevated lactate peaks were seen in 24 patients (48%), notably in neurocysticercosis (active stage) and abscesses.
• Reduced NAA was recorded in 6 patients (12%).
• Cho/Cr >2 was observed in 8 patients (16%), correlating with high-grade neoplastic lesions in most cases.
• Abscesses demonstrated amino-acid resonances with lactate.

Follow-up imaging in 26 patients showed resolution of lesion and perilesional edema consistent with favorable response to specific medical therapy (antitubercular therapy for tuberculomas, antiparasitic and anti-inflammatory management for NCC, antibiotics/drainage when indicated for abscess).

This prospective study of 50 patients demonstrates that 1H-MRS provides valuable metabolic information that complements conventional MRI and other advanced sequences (DWI, SWI/perfusion) in differentiating ring-enhancing intracranial lesions.

Utility in distinguishing tuberculoma and neurocysticercosis

A recurring diagnostic challenge is distinguishing tuberculoma from neurocysticercosis since both may be multiple and occur at the gray-white junction. In our cohort, tuberculomas consistently exhibited significant lipid peaks likely reflecting mycobacterial cell wall lipid components; Cho/Cr typically ranged [1–2]. In contrast, NCC frequently showed elevated lactate and succinate with negligible lipid resonance in active stages — findings consistent with anaerobic metabolism and parasitic degradation products. These metabolic signatures can meaningfully guide clinicians in initiating appropriate medical therapy (antitubercular treatment vs antiparasitic/anti-inflammatory regimens) without immediate invasive diagnostic procedures[7-10].

Neoplastic vs infectious lesions

Elevated choline and reduced NAA were characteristic of neoplastic lesions and correlated with histologic or clinical diagnoses of primary and metastatic tumors; Cho/Cr >2 was particularly suggestive of higher-grade pathology. Conversely, abscesses frequently exhibited amino-acid peaks and lactate — a profile that favors infectious etiology and supports antibiotic therapy and consideration for drainage[12-14].

Clinical implications for treatment planning

MRS-directed differentiation can shorten diagnostic delay, reduce unnecessary neurosurgical interventions, and guide early institution of disease-specific therapies (e.g., antitubercular drugs, antiparasitics, antibiotics, or oncologic referral). Moreover, MRS is noninvasive and repeatable, useful for follow-up to document treatment response as observed in 26 patients with lesion resolution[1,8,16].

Limitations

• Single-center study with modest sample size limits generalizability.
• Single-voxel MRS at 1.5 T may miss metabolic heterogeneity within lesions; multi-voxel (CSI) at higher field strength (3T) might provide additional information.
• Lack of histopathologic confirmation for all lesions — in many infectious lesions diagnosis was clinicoradiological and therapeutic response–based.
• MRS acquisition, processing and interpretation lack universal standardization; inter-operator variability and voxel-placement issues may affect spectra.
  Future larger, multicenter studies with standardized MRS protocols and correlation with pathology will help validate thresholds (e.g., Cho/Cr cutoffs) and develop reproducible diagnostic criteria.

This prospective study of 50 patients demonstrates that 1H-MRS provides valuable metabolic information that complements conventional MRI and other advanced sequences (DWI, SWI/perfusion) in differentiating ring-enhancing intracranial lesions.

Utility in distinguishing tuberculoma and neurocysticercosis

A recurring diagnostic challenge is distinguishing tuberculoma from neurocysticercosis since both may be multiple and occur at the gray-white junction. In our cohort, tuberculomas consistently exhibited significant lipid peaks likely reflecting mycobacterial cell wall lipid components; Cho/Cr typically ranged [1–2]. In contrast, NCC frequently showed elevated lactate and succinate with negligible lipid resonance in active stages — findings consistent with anaerobic metabolism and parasitic degradation products. These metabolic signatures can meaningfully guide clinicians in initiating appropriate medical therapy (antitubercular treatment vs antiparasitic/anti-inflammatory regimens) without immediate invasive diagnostic procedures[7-10].

Neoplastic vs infectious lesions

Elevated choline and reduced NAA were characteristic of neoplastic lesions and correlated with histologic or clinical diagnoses of primary and metastatic tumors; Cho/Cr >2 was particularly suggestive of higher-grade pathology. Conversely, abscesses frequently exhibited amino-acid peaks and lactate — a profile that favors infectious etiology and supports antibiotic therapy and consideration for drainage[12-14].

Clinical implications for treatment planning

MRS-directed differentiation can shorten diagnostic delay, reduce unnecessary neurosurgical interventions, and guide early institution of disease-specific therapies (e.g., antitubercular drugs, antiparasitics, antibiotics, or oncologic referral). Moreover, MRS is noninvasive and repeatable, useful for follow-up to document treatment response as observed in 26 patients with lesion resolution[1,8,16].

Limitations

• Single-center study with modest sample size limits generalizability.
• Single-voxel MRS at 1.5 T may miss metabolic heterogeneity within lesions; multi-voxel (CSI) at higher field strength (3T) might provide additional information.
• Lack of histopathologic confirmation for all lesions — in many infectious lesions diagnosis was clinicoradiological and therapeutic response–based.
• MRS acquisition, processing and interpretation lack universal standardization; inter-operator variability and voxel-placement issues may affect spectra.
  Future larger, multicenter studies with standardized MRS protocols and correlation with pathology will help validate thresholds (e.g., Cho/Cr cutoffs) and develop reproducible diagnostic criteria.

1. Garg RK, Sinha MK. Multiple ring-enhancing lesions of the brain. J Postgrad Med. 2010;56(4):307–316.
2. Shetty G, Avabratha KS, Rai BS. Ring-enhancing lesions in the brain: A diagnostic dilemma. Iran J Child Neurol. 2014;8(3):61–64.
3. Elsadway ME, Ibrahim Ali H. Verification of brain ring enhancing lesions by advanced MR techniques. Alexandria J Med. 2018;54(2):167–171.
4. Choudary GP, Lakshmi AY, Bodagala VL, Chandra VV, Thota N, Chowhan AK. Perfusion-weighted imaging in differentiating ring-enhancing lesions in brain. J Dr NTR Univ Health Sci. 2019;8(3):162–169.
5. Condon B. Magnetic resonance imaging and spectroscopy: How useful is it for prediction and prognosis? EPMA J. 2011;2(4):403–410.
6. Mishra AM, Gupta RK, Jaggi RS, Reddy JS, Jha DK, Husain N, et al. Role of diffusion-weighted imaging and in vivo proton magnetic resonance spectroscopy in the differential diagnosis of ring-enhancing intracranial cystic mass lesions. J Comput Assist Tomogr. 2004;28(4):540–547.
7. Alam MS, Sajjad Z, Hafeez S, Akhter W. Magnetic resonance spectroscopy in focal brain lesions. J Pak Med Assoc. 2011;61(6):540–543.
8. Hellström J, Romanos ZR, Libard S, Wikström J, Ortiz-Nieto F, Alafuzoff I, et al. The value of magnetic resonance spectroscopy as a supplement to MRI of the brain in a clinical setting. PLoS One. 2018;13(11):e0207336.
9. Verma SR, Choudhary N, Sardana V. Magnetic resonance spectroscopy in differentiation of intracranial tuberculoma and neurocysticercosis. Int J Sci Res. 2017;6(3):397–399.
10. Morales H, Alfaro D, Martinot C, Fayed N, Gaskill-Shipley M. MR spectroscopy of intracranial tuberculomas: A singlet peak at 3.8 ppm as potential marker to differentiate them from malignant tumors. Neuroradiol J. 2015;28(3):294–302.
11. Sharma BB, Sharma S. Neurocysticercosis (NCC) vs central nervous system (CNS) tuberculoma in children — Dilemma over clinico-radiological diagnosis? Open J Pediatr. 2016;6(3):245–251.
12. Pretell EJ, Martinot C, Garcia HH, Alvarado M, Bustos JA, Martinot C. Differential diagnosis between cerebral tuberculosis and neurocysticercosis by magnetic resonance spectroscopy. J Comput Assist Tomogr. 2005;29(1):112–114.
13. Parry A, Wani A, Shaheen F, Wani A, Feroz I, Ilyas M. Evaluation of intracranial tuberculomas using diffusion-weighted imaging, magnetic resonance spectroscopy and susceptibility weighted imaging. Br J Radiol. 2018;91(1091):20180342.
14. Venkat B, Aggarwal N, Makhaik S, Sood R. A comprehensive review of imaging findings in human cysticercosis. Jpn J Radiol. 2016;34(4):241–257.
15. Yuzawa H, Hirose Y, Kimura T, Kimura S, Sugawara H, Yanagisawa A, et al. A case of cerebral tuberculoma mimicking neurocysticercosis. Acute Med Surg. 2017;4(3):329–333.
16. Kaddah RO, Khalil ME. Malignant focal brain lesions: Value of MRS tumor biomarkers in preoperative prediction of grades of malignancy. Egypt J Radiol Nucl Med. 2014;45(4):1201–1208.
17. Fan G, Sun B, Wu Z, Guo Q, Guo Y. In vivo single-voxel proton MR spectroscopy in the differentiation of high-grade gliomas and solitary metastases. Clin Radiol. 2004;59(1):77–85.
18. Niekerk M, Goussard P, Toorn R, Solomons R. Giant cerebral tuberculoma mimicking a high-grade tumour in a child. BMJ Case Rep. 2022;15(4):e248545.
19. Ostojić J, Kozić D, Grujičić D, Georgievski-Brkić B, Dragičević D, Boban J. N-acetylaspartate-like peak on MR spectroscopy: A useful clue for brain metastases originating from mucin-expressing primary tumors. Front Neurol. 2022;13:987654.