European Journal of Cardiovascular Medicine

A diagnostic challenge existed for clinicians until the previous century because the skull was sealed. The imaging of the CNS (Central Nervous System) has undergone remarkable changes in the past century. Magnetic resonance imaging's developments have affected all aspects of neuroscience practice overall and the treatment of intra-axial brain lesions specifically. One common type of neuroimaging abnormality is a “ring-enhancing lesion." These are lesions that appear as central non-enhancing areas with a bright peripheral rim of enhancement on MRI or CT images after contrast dye is applied.[1] Cross sectional imaging modalities are the first to detect the symptoms of an intracranial space-occupying lesion in a patient who comes to the hospital. It can be caused by various etiologies, such as brain abscesses, tuberculoma, cystic metastasis, primary brain tumors, infarcts, and lymphomatous tumors. Most of the lesions are located at the interface between gray and white matter and subcortical areas. The main reason for multiple ring-enhancing lesions in the brain in India is infectious diseases. Tuberculosis is the most common infection, followed by neurocysticercosis. Some non-infectious diseases that can cause these lesions are neoplastic disorders. The majority of neoplastic brain lesions are secondary to a systemic neoplastic illness.[2] For intracranial abscesses, medical management strategies are antibiotics or drainage, and for neoplasms, they are surgery and biopsy. This poses a serious neurosurgical challenge that requires us to diagnose correctly.[1] MRI can find more than 90% of brain lesions of different kinds, while CT only finds 77%. MRI is safer and less invasive than CT since it does not need iodine-based contrast agents or X-rays that cause radiation. This makes MRIs better for children and older people.[2] But conventional MRI is less accurate, with only about 61.4% sensitivity in detecting neoplasms from abscesses. So, we use advanced imaging methods like the diffusion-weighted method that detects restriction and spectroscopy that identifies metabolites as an extra aid for better diagnosis.[3] Diffusion imaging is an advanced technique of imaging that measures the movement of water molecules in tissues and can detect vascular territory infarcts, tumors, epilepsy, and white matter disorders by calculating the apparent diffusion coefficient value. Magnetic resonance spectroscopy can also characterize the lesion by measuring the altered levels of metabolites.[4] These noninvasive investigations help us avoid needless intervention, provide a quick and precise diagnosis, and improve the patient’s outcome.[5] The latest advances in MRI include ultra-fast scanners and contrast agents that are sensitive to metabolic changes. For MRS imaging, 3 Tesla scanners are the standard. However, using 4 Tesla or 4.7 Tesla scanners can improve our diagnosis, as they have higher sensitivity than 3 Tesla due to their stronger field strength. To overcome the limitations of gradient performance, 7 Tesla scanners are being developed. With hyperpolarized MRI and metabolic contrast, we can map the rates of enzymatic reactions. This will have a significant impact on the future of MR spectroscopy and its technical development. Consequently, various research studies will be possible with these emerging techniques of MRS. [6]

Aims and Objectives

• To assess the usefulness of diffusion-weighted imaging and magnetic resonance spectroscopy in diagnosing intracranial peripherally enhancing lesions.
• To study characteristic imaging findings of various ring-enhancing lesions by MRI sequences with contrast.
• To differentiate ring-enhancing brain lesions using DWI (Diffusion-Weighted Imaging) and ADC (Apparent Diffusion Coefficient) values.
• To study the role of MR spectroscopy in the evaluation of various ring-enhancing lesions.
• To analyze the efficacy of MRI in adjunct with DWI and MRS in correctly diagnosing the ring-enhancing lesions with histopathological correlation or follow up wherever possible

This was a hospital-based observational prospective study conducted among 68 patients with the diagnosis of cerebral ring enhancing lesions at the Department of Radiodiagnosis at Shri B.M. Patil Medical College, Hospital and Research Centre, BLDE (DU), situated at Vijayapura, Karnataka, from September 2022 to April 2024, after obtaining clearance from the institutional ethics committee and written informed consent from the study participants.

Inclusion Criteria

• Patients with intracranial ring enhancing lesions, which are detected on contrast MR studies and are taken up prospectively.
• Patients of all age groups [both males and females].

Exclusion Criteria

• Patients having contraindications to intravenous contrast agents.
• Patient having history of fear of closed spaces [claustrophobia].
• Patient with a prior history of any metallic implants inside the body or any pacemakers in situ.

Statistical Methods

Data was entered in a Microsoft Excel data sheet, and analysis was done using SPSS 22.0 version software. Mean ± SD [Min-Max] was calculated for results. The results of the cases were presented in number [percentage]. Descriptive statistics, frequencies, and proportions were calculated and tabulated. Sensitivity, specificity, negative predictive value, and positive predictive value were calculated using SPSS software. MR spectroscopy with DWI values and their diagnostic accuracy were also determined. The Chi square test, Fisher exact test, and one sample student’s t-test were the tests of significance for categorical data. A p-value <0.05 was considered statistically significant.

In the study, NAA was decreased in 50% of patients with metastasis, neurocysticercosis, 71% of patients with primary brain tumors, and 52.6% of patients with tuberculoma, and increased in 50% of patients with cerebral abscess. There was a significant difference in NAA change with respect to diagnosis.

Cho was increased in 50% of patients with cerebral abscess and metastasis, in 100% of patients with neurocysticercosis and primary brain tumors, and in 78.9% of patients with tuberculomas. There was a significant difference in Cho with respect to the diagnosis.

Similarly, lip-lac was increased in 100% of patients with cerebral abscess and tuberculoma, 30% of patients with metastasis and primary brain tumors, and 50% of patients with neurocysticercosis. There was a significant difference in lip-lac change with respect to diagnosis.

Creatine was decreased in 12.9% of subjects with primary brain tumors and 10.5% of patients with tuberculoma. There was a significant difference in creatine change with respect to diagnosis.

The mean Cho/Cr ratio was high in primary brain tumors [4.3 ± 0.36], followed by metastasis and tuberculoma.

The mean Cho/NAA ratio was high in primary brain tumors [1.7 ± 1.3], followed by tuberculoma and metastasis.

The mean NAA/Cho ratio was high in cerebral abscess [1.65± 0.06] and low in primary tumors.

The mean NAA/Cr ratio was high in cerebral abscess [2.2± 0.06], followed by metastasis.

There was a significant difference in the mean Cho/Cr, Cho/NAA ratio, NAA/Cho, and NAA/Cr with respect to diagnosis.

Sex Distribution

68 patients were evaluated, with an incidence higher in males than females. 42 were males (61.8%) and 26 were females (38.2%).

Age Distribution

Among 68 patients, the age range was from 0 to 84 years, of which the majority  were in the age groups of 70+ years and 40 to 49 years [25% and 20.6%, respectively], and the least were in the age group < 10 years.

Clinical Features

Headache was the most common complaint in 60.3% of cases. Giddiness (26.5%), altered sensorium (23.5%), seizures (20%), vomiting (20%), and fever (10%) were the other presenting complaints.

Pathologies

Primary brain tumors [45.6%] were the most common pathology among the 68 individuals investigated. This was followed by tuberculomas [27.9%], metastasis [14.7%], cerebral brain abscess [5.9%], and NCC [5.9%].

The increased prevalence of tuberculomas is probably because tuberculosis is more common in poorly developed countries like India. Primary brain tumors followed by metastasis were the most common causes of intracranial ring-enhancing lesions, as depicted in the study done by Schwartz et al.[7]

Side of Lesion

In the 58 individuals with ring-enhancing lesions in the brain, 30 [44.1%] had lesions on the right side, 20 [29.4%] had bilateral lesions, and 18 [26.5%] had lesions on the left side.

Our study was in accordance with the study performed by Patil et al.[8] 50 patients with intracranial ring-enhancing lesions were studied; 18 patients [36%] had a right-sided lesion, 16 patients [32%] had a lesion on the left side, and 16 patients [32%] had a lesion bilaterally.

Number of Lesions

Out of 68 patients evaluated, 12 patients [17.6%] showed 2–5 lesions in the brain, while 42 patients [61.8%] presented with a single lesion in the brain. More than five lesions were seen in 14 cases [20.6%]. Most of the patients presented with a single intracranial lesion in our study.

Size of the Lesion

The majority of the patients, 37 [54.4%] had lesions that were between 2-4 cm in size, 16 [23.5%] had lesions that were less than 2 cm in size, and 15 [22.1%] had lesions that were more than 4 cm in size.

This was in accordance with the study performed by Garg et al.[9] where thirty patients with intracranial ring-enhancing lesions were studied, and 66.6% had a lesion size ranging between 2-4 cm, while 20% had a lesion size measuring less than 2 cm, and 13.3% of the total patients had a lesion size measuring more than 4 cm.

Location of Lesions

Among the 68 patients evaluated, the maximum ring-enhancing lesions in the brain were located in the fronto-parieto-temporal region in 23 cases and least in the cerebellum (3 cases) and tempor-occipital regions (1 case).

T1 Morphology

Out of 68 patients studied, a maximum 34 cases [50%] showed homogenous hypointesity [similar to CSF intensity] on T1-weighted images. 8 cases [11.8%] were isointense, heterogeneously hypointense in 26 cases [38.2%].

T2 Morphology

Out of 68 cases on T2W images, 52 cases [76.4%] were hyperintense, while 14 cases [20.6%] were hypointense on T2W in our study, and 2 cases [2.9%] were isointense.

Diffusion Restriction

Among the 68 patients evaluated, 51 patients [75%] show diffusion-restricting lesions [partial or complete] and 17 patients [25%] show no diffusion restriction. All the lesions diagnosed as abscesses showed complete diffusion restriction, high DWI, and correspondingly low ADC. This was in accordance with the study performed by Luthra et al,[10] where 110 patients were retrospectively analyzed and classified into tubercular, pyogenic, and fungal abscesses. They stated that both pyogenic and tubercular abscesses show complete diffusion restriction with high DWI and correspondingly low ADC in the wall and cavity of the lesion, while the fungal abscesses show restriction in the wall and fungal hyphae within.

MRS

Choline peak was identified in 57 cases [83.8%] of the 68 individuals studied, lipid-lactate in 38 cases [55.9%], and decreased NAA peak in 39 cases [57.4%]. Creatine was increased in 38 cases [54.4%].

Our study was not in accordance with the study performed by Patil et al.,[8] where 50 patients were studied for intracranial ring-enhancing lesions, out of which the majority of patients showed a choline peak in 32 patients (64%), followed by a lipid peak in 28 patients (56%), a lactate peak in 26 patients [52%], a reduced NAA peak in 16 patients (32%), and amino acids in 7 patients [14].

Various Pathologies and Their Respective MRI, MRS and DWI Characteristics

The diagnosis of the lesions on imaging was confirmed by microscopic examination of culture and histopathological examination of surgically aspirated or excised lesions.

Tuberculoma

Out of sixty-eight patients evaluated, tuberculomas were seen in 19 (27.9%) cases. Among the 19 cases (males = 13; females = 6), Single lesions were noted in 7 cases (36.8%) and multiple lesions in 12 cases (63.2%). They are seen as conglomerate lesions that are hypointense on T1-weighted images. They may show partial or complete restriction, as seen in 13 cases (68%).

This is in accordance with findings in tuberculoma done by Maheshwarappa et al.[11] According to that study, caseating necrotic lesions didn’t show any diffusion restriction. While the perilesional area just adjacent to the wall of the lesion shows restricted diffusion.

The lesions may show a nodular or irregular ring-like enhancement. All our cases presented with ring like enhancement. Nodular enhancement is also seen in three cases in addition to the ring-enhancing lesions. MRS showed a lipid peak in 19 (100%) cases, and it plays an important role in identifying tuberculomas from other infective granulomas.

The stage of the tuberculoma, whether it is caseous or non-caseous, can also be identified on an MRI with the help of T2-weighted images. Post-contrast images are very helpful in identifying the size of the tuberculomas due to their excellent spatial resolution, which differentiates the granuloma from its surrounding edema.

Tae Kyoung Kim, Kee Hyun Chang, Chong Jai Kim, Jin Mo Goo, Myeong Cherl Kook, and Moon Hee Han (1995) showed that on T1-weighted images, the granulomas showed a slightly hyperintense rim. On T2-weighted images, the entire portion of the granuloma showed slightly heterogeneous isointensity or hypointensity with small, markedly hypointense foci. On postcontrast T1-weighted images, there were single or multiple conglomerate ring enhancements within a tuberculoma in all six patients.[12]

Cr and NAA: Cho ratio in our study is similar to the study conducted by Pretell et al,[13] in which ten patients were included: four cases of tuberculoma and six cases of NCC. MRS was done in all patients who showed a high lipid peak and reduced NAA and creatine in tuberculoma. It also showed that the Cho: Cr ratio was >1 in all cases of tuberculoma and <1 in all cases of NCC.

Neurocysticercosis

Out of 68 patients evaluated, neurocysticercosis was seen in 4 cases (males = 0; females = 4). All four patients presented with multiple lesions. All the cases showed intraparenchymal forms of NCC with no spinal cysticercosis or subarachnoid cysticercosis. MRS shows a choline peak, and two cases showed an elevated NAA peak. All the lesions were hypo- to isointense on T1-weighted images, and two were hyperintense on T2. All four cases showed diffusion restrictions on DWI. Intense ring enhancement with surrounding perilesional edema was seen in all cases, suggesting active lesions. The Cho/Cr ratio was less than 1.1 in 2 cases of NCC and more than 1.2 in all tuberculomas, which is similar to the study performed by Kumar et al. and Jayasunder et al.[14,15]

We did not find any cases of intraventricular cysticercosis, possibly due to the tiny sample size of the study. Martinez et al.,[16] reported intraventricular neurocysticercosis in 22% of cases.

As compared to Suss et al.,[17] our investigation showed parenchymal cysticercosis was better recognized on MRI than CT. The characteristics of parenchymal types of NCC in our investigation are comparable to those found in Amaral et al.[18]

Abscess

Out of the 68 patients, abscesses were found in 4 cases (males = 3; females = 1). A single abscess was found in two cases, whereas the other two cases had multiple abscesses. Two cases showed a size < 2 cm, and two cases were 2-4 cm in size. All were hypointense on T1-weighted images with a hyperintense rim, as noted in all 4 patients, and were hyperintense on T2-weighted images with a surrounding hypointense rim (all 4 cases). They showed complete diffusion restriction, and MRS showed a lactate peak in all 4 cases, suggesting anaerobic glycolysis.

The appearance of abscesses on MR was described by Haimes et al.[19] We compared our findings to those previously published and identified peripheral edema, central necrosis, and the abscess capsule's typical pattern of peripheral enhancement.

Our study was also in accordance with a study performed by Lai et al.[20] that stated that metabolite ratios studied on MRSI show that the maximum Cho/Cr and Cho/NAA ratios of the contrast-enhancing rim were significantly higher in GBM as compared to abscess, thus useful in differentiating the two.

Brain Metastasis

Out of the 68 patients, 10 cases were metastases (males = 6; females = 4). Multiple lesions were identified in 7 cases and single lesions in 3 cases. All the cases showed high Cho and Cr levels. Six cases were heterogenously hyperintense on T2 with peripheral rim FLAIR hyperintensities. A thick, irregular type of ring enhancement was noted after contrast administration. Our findings were similar in comparison to the study performed by Vieth RG et al.[21]

Shetty et al.[22] concluded that a diffusion-weighted MRI sequence can help in differentiating between metastatic and infective ring-enhancing lesions like abscesses. In our study, it was observed that the Ch/Cr [p value<.0001] and Ch/NAA [p value=.0001] ratios were statistically significant in differentiating the two REL`s. The Ch/Cr and Ch/NAA ratios were significantly elevated in cases of metastasis.

All patients showed a high choline peak and an increased lipid lactate peak, with significantly reduced NAA and creatine peaks. These findings are similar to those of the study done by Chernov et al.[23] In that study, tumor lesions showed statistically significantly reduced NAA and creatine, while choline and lipid-lactate peaks were present. On MRS imaging, all of the patients had high Cho:Cr and Cho:NAA levels, as well as a lower NAA:Cr and NAA:Cho ratio. Following contrast injection, a thick, uneven kind of ring enhancement was seen.

Primary Brain Tumor

Out of the 31 cases of primary brain tumors included in this study, 29 were glioblastomas, and 2 were pilocytic astrocytomas. All cases of glioblastomas showed a thick, irregular type of ring enhancement with extensive non-enhancing central necrosis. A thick, irregular, enhancing cyst wall with mural nodules was seen in the case of pilocytic astrocytoma.

All primary brain tumors appeared hypointense on T1. 3 cases appeared hypointense on T2, with 28 cases appearing hyperintense on T2. Out of the 31 cases, 23 cases showed complete or partial diffusion restriction in the solid portion of the lesion.

Smirniotopoulos et al.[2] from Bethesda in 1996 concluded that the most common imaging appearance of glioblastoma multiforme is a large heterogeneous mass in supratentorial white matter that exerts a considerable mass effect.

MRS (Magnetic Resonance Spectroscopy), along with diffusion-weighted imaging, helps in differentiating and characterizing the ring enhancing lesions in the brain. That leads to an accurate diagnosis of the disease. Tuberculoma can be differentiated from NCC by a high Cho:Cr ratio [1.2–2.0] and conglomerated ring enhancement in tuberculoma. Tuberculoma can be differentiated from metastasis by a high Cho:Cr ratio in metastasis (more than 2.0) compared to tuberculoma. Metabolites like amino acids, succinate, aspartate, and acetate on MRS can help to differentiate pyogenic abscesses from tubercular abscesses. Multiple lesions, disproportionately large perilesional edema, and a and a high elevation of the choline peak with reduced creatinine and NAA help in the better identification of metastatic lesions. T2WI helped in differentiating caseating tuberculoma with a liquefied center from caseating tuberculoma with a non-liquefied center. DWI is useful for differentiating brain infections [brain abscess, tuberculoma, and NCC] from secondary brain metastases. A complete diffusion restriction on DWI is highly suggestive of brain abscess over metastatic lesions and tuberculoma. With the help of MRI, the precise anatomical location and extent of lesions can be identified. MRS is not the only criteria for diagnosing ring-enhancing lesions. The combination of MRS and diffusion-weighted imaging has yielded synergetic potency in detecting various ring-enhancing lesions, leading to accurate diagnosis and thus helping in management and prognosis

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