The role of diffusion-weighted magnetic resonance imaging in the differential diagnosis of intracranial non-ischemic lesions

Abstract

AimDiffusion-weighted imaging (DWI) provides complementary information to conventional magnetic resonance imaging (MRI), but its diagnostic contribution in non-ischemic intracranial lesions remains incompletely defined. This study evaluated DWI and apparent diffusion coefficient (ADC) characteristics of various non-ischemic intracranial lesions. MethodsThis retrospective study included 71 patients in whom 122 intracranial non-ischemic lesions were identified. To ensure independent observations, one index lesion per patient was included in the comparative DWI analyses, resulting in 71 patient-level imaging observations. DWI signal intensities and ADC map findings were qualitatively categorized, and lesion walls were evaluated separately. Group comparisons were performed using the chi-square test or Fisher’s exact test ResultsArachnoid cysts were uniformly hypointense and epidermoid cysts uniformly hyperintense on DWI (P < .001). All brain abscesses showed marked DWI hyperintensity with corresponding ADC hypointensity. Primary tumors (66.7%) and metastases (55.6%) frequently showed DWI hyperintensity but had heterogeneous diffusion patterns. Demyelinating lesions were predominantly hyperintense (80%), whereas infectious and encephalitic lesions showed variable findings. DWI signal distributions did not differ significantly between abscesses and primary tumors or metastases (P > .05). Abscess walls were hypointense, whereas tumor walls were predominantly hyperintense on DWI. ConclusionDWI is particularly useful for differentiating arachnoid from epidermoid cysts and for demonstrating restricted diffusion in brain abscesses. However, overlap between infectious and neoplastic lesions limits its standalone diagnostic value. Integrating DWI and ADC findings with lesion morphology, wall characteristics, conventional MRI, and clinical data may improve diagnostic confidence.

Keywords

Introduction

Magnetic resonance imaging (MRI) is central to the evaluation of intracranial non-ischemic lesions, including cystic, neoplastic, infectious, and demyelinating disorders.^1,2 Conventional T1-weighted, T2-weighted, and fluid-attenuated inversion recovery sequences provide anatomical and morphological information; however, lesions with similar localization, edema, enhancement, or wall characteristics may remain difficult to distinguish.^3,4
Diffusion-weighted imaging (DWI) reflects water-molecule mobility and tissue microstructure, while apparent diffusion coefficient (ADC) maps support interpretation of diffusion restriction^5-13 Beyond acute ischemia, DWI is used in tumors, abscesses, demyelinating disease, and encephalitis.^14-17 It is particularly useful for distinguishing epidermoid from arachnoid cysts and brain abscesses from necrotic or cystic tumors, although overlapping diffusion patterns may limit specificity.^18,19
This study evaluated DWI and ADC signal patterns in intracranial non-ischemic lesions, including lesion core and wall characteristics, to determine their contribution to differential diagnosis beyond conventional MRI.

Materials and Methods

Study Design and Study Population This retrospective observational study was conducted in accordance with the principles of the Declaration of Helsinki. The manuscript was prepared and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. The requirement for obtaining individual informed consent was waived by the Gaziantep University Faculty of Medicine Ethics Committee because of the retrospective study design and the use of anonymized imaging and clinical data. A retrospective search of the institutional radiology information system and picture archiving and communication system was performed to identify cranial MRI examinations obtained between December 2004 and June 2009 for patients referred from the neurology, pediatrics, oncology, and neurosurgery departments. A total of 71 patients (32 females and 39 males; mean age, 28.4 ± 18.7 years; age range, 0–65 years) with intracranial non-ischemic lesions were included in the study. Potentially eligible patients were initially identified from MRI reports indicating an intracranial lesion other than acute cerebral ischemia. The corresponding MRI examinations and available clinical records were subsequently reviewed to determine eligibility. All consecutive patients who met the predefined eligibility criteria were included. The inclusion criteria were the presence of at least one intracranial non-ischemic lesion on conventional MRI and the availability of both conventional MRI and diffusion-weighted imaging sequences. Following application of the eligibility criteria, 71 patients with a total of 122 intracranial non-ischemic lesions were included. For patients with multiple lesions, the largest evaluable lesion based on maximal axial diameter was designated as the index lesion; therefore, one index lesion per patient (n = 71) was included in the comparative imaging analyses. Lesion Classification Final diagnoses were established using radiological, histopathological, clinical, and laboratory information, as appropriate for each lesion category; DWI findings were not used as the sole diagnostic reference. Arachnoid and epidermoid cysts were diagnosed radiologically on the basis of their characteristic location, morphology, and conventional MRI signal features, with DWI used as supportive information. Primary brain tumors were confirmed histopathologically following biopsy or surgical resection. Metastatic lesions were confirmed histopathologically when tissue was available; otherwise, diagnosis was based on a documented primary malignancy, compatible intracranial imaging findings, and clinical or radiological follow-up. Demyelinating lesions were diagnosed by the neurology team using the clinical course and characteristic conventional MRI findings, supported by cerebrospinal fluid or laboratory findings when available. Brain abscesses and meningitic or encephalitic lesions were diagnosed using compatible clinical and conventional MRI findings together with available cerebrospinal fluid, microbiological, serological, operative, and treatment-response data. Subacute sclerosing panencephalitis was diagnosed using compatible clinical and neurological findings supported by electroencephalographic and measles-antibody findings, whereas glutaric aciduria type 2 was diagnosed using clinical findings and disease-specific biochemical or metabolic testing. MRI Acquisition Protocol DWI was acquired using a single-shot spin-echo echo-planar sequence (TR/TE, 4779/81 ms; matrix, 128 × 256; field of view, 25 cm; slice thickness, 5 mm; gap, 1 mm). Diffusion gradients were applied in three orthogonal directions with b-values of 0 and 1000 s/mm². Acquisition time was approximately 25–40 seconds, and ADC maps were generated automatically. Diffusion-Weighted Imaging (DWI) Diffusion-weighted imaging was performed using a single-shot spin-echo echo-planar imaging (EPI) sequence. The acquisition parameters were as follows: repetition time (TR) of 4779 ms, echo time (TE) of 81 ms, matrix size of 128 × 256, field of view (FOV) of 25 cm, slice thickness of 5 mm, and an inter-slice gap of 1 mm. Diffusion-sensitizing gradients were applied simultaneously in three orthogonal directions to generate trace images. Two b-values (0 and 1000 s/mm²) were used for diffusion weighting. The total acquisition time for DWI ranged between approximately 25 and 40 seconds. Apparent diffusion coefficient (ADC) maps were automatically generated for quantitative assessment of diffusion characteristics. Image Analysis All MRI examinations were independently evaluated by two radiologists with 8 and 12 years of experience, respectively, in cranial MRI and diffusion-weighted imaging interpretation. During image assessment, the radiologists were blinded to each other’s evaluations and, where applicable, to the final clinical and histopathological diagnoses. Conventional MRI sequences were assessed for lesion number, size, anatomical location, signal characteristics on T1-weighted, T2-weighted, and FLAIR images, and the presence, morphology, and contrast-enhancement pattern of the lesion wall. Each radiologist independently categorized lesion signal intensity on DWI relative to cerebrospinal fluid as markedly hypointense, mildly hypointense, isointense, mildly hyperintense, or markedly hyperintense. ADC maps were evaluated to support the interpretation of diffusion restriction. The lesion core and wall were assessed separately. After completion of the independent evaluations, disagreements regarding lesion signal category or wall characteristics were reviewed jointly by the two radiologists and resolved by consensus. The consensus classifications were used in the final statistical analyses. Because this was a retrospective study that included all eligible patients identified during the predefined study period, no a priori sample size calculation or formal statistical power analysis was performed. The sample size was determined by the number of eligible cases available in the institutional records. Statistical Analysis All statistical analyses were performed using IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA) and R software version 4.3.0 (R Foundation for Statistical Computing, Vienna, Austria). Demographic and diagnostic distributions were summarized at the patient level. Comparative analyses of DWI signal characteristics were performed using one index lesion per patient, ensuring that no patient contributed more than one observation. The chi-square test or Fisher’s exact test was used, as appropriate, to compare categorical DWI findings between diagnostic groups. A P value < 0.05 was considered statistically significant. Ethical Approval The study protocol was approved by Ethics Committee of Gaziantep University Faculty of Medicine (Date: 2009.02.14, No: 02-2009/26).

Results

The study population consisted of 32 females and 39 males. The mean age was 28.4 ± 18.7 years, and the age range was 0–65 years. The study included 71 patients with a total of 122 intracranial non-ischemic lesions. Patient-based diagnostic categories are presented in Table 1. For the comparative imaging analyses, one index lesion per patient was evaluated, yielding 71 independent imaging observations. Arachnoid cysts were the most frequent patient-level diagnosis (19/71, 26.8%), followed by primary brain tumors (15/71, 21.1%) and metastatic tumors (9/71, 12.7%) (Table 1). Diffusion-weighted imaging (DWI) provided clear diagnostic differentiation (Table 2). Arachnoid cysts were uniformly hypointense (100%), whereas epidermoid cysts and brain abscesses showed consistent marked hyperintensity (100%). In contrast, primary tumors (66.7% hyperintense) and metastases (55.6% hyperintense) demonstrated heterogeneous diffusion patterns. Demyelinating and encephalitic lesions were predominantly hyperintense, although some variability was observed (Table 2). In primary tumors (n = 15), the lesion wall was hyperintense in 10 cases (66.7%) and hypointense in 5 cases (33.3%) on DWI, whereas ADC findings were predominantly isointense (53.3%). Metastatic lesions (n = 9) demonstrated hyperintense walls in 5 cases (55.6%) and hypointense in 4 cases (44.4%) on DWI, with ADC maps showing hyperintensity in 6 cases (66.7%). All brain abscesses (n = 3) exhibited hypointense lesion walls on both DWI and ADC maps (100%). Among non-neoplastic lesions, demyelinating lesions (n = 5) were predominantly hyperintense on DWI (80%), while herpes encephalitis (n = 3) showed hyperintense lesion walls in all cases (100%). Tuberculous meningitis (n = 3) demonstrated mainly hyperintense walls on DWI (66.7%). In contrast, bacterial meningitis (n = 2) showed isointense lesion walls on DWI (100%) and hypointensity on ADC maps (100%). Non-specific viral encephalitis (n = 5) was predominantly isointense on DWI (60%), with variable ADC findings. The statistical comparison of diffusion-weighted imaging (DWI) signal intensities between major lesion categories is presented in Table 3. No statistically significant difference was observed between brain abscesses and primary tumors (P = .407) or between abscesses and metastatic lesions (P = .301). Similarly, there was no significant difference in DWI signal intensity distribution between primary tumors and metastases (P = .562). In contrast, a statistically significant difference was found between arachnoid cysts and epidermoid cysts (P < .001) (Table 3). In a 1-year-old female patient diagnosed with a brain abscess, axial diffusion-weighted imaging (DWI), On the ADC map, increased signal intensity was observed in the adjacent brain parenchyma, consistent with perilesional edema (Figure 1). In a 66-year-old female patient diagnosed with an epidermoid cyst, imaging at the level of the cerebellopontine angle demonstrated a lesion in the left cerebellopontine region (Figure 2). In a 43-year-old female patient diagnosed with meningioma, axial sections at the level of the centrum semiovale demonstrated a parasagittal lesion on the left side that appeared hyperintense on T2-weighted imaging (A) and mildly hyperintense on FLAIR (B). The lesion was hypointense on pre-contrast T1-weighted imaging (C) and showed diffuse enhancement on contrast-enhanced T1-weighted images (D). On diffusion-weighted imaging (DWI) (E), the lesion demonstrated hyperintensity, while the apparent diffusion coefficient (ADC) map (F) showed isointensity (Figure 3).

Discussion

This study showed that DWI clearly differentiated arachnoid from epidermoid cysts and consistently demonstrated restricted diffusion in brain abscesses. In contrast, primary tumors, metastases, and infectious or demyelinating lesions had heterogeneous diffusion patterns. DWI signal intensity alone did not distinguish abscesses from neoplastic lesions, whereas assessment of lesion walls provided additional diagnostic information.
Our finding that DWI is highly useful in differentiating epidermoid cysts from arachnoid cysts is consistent with previous studies. Tsuruda et al. first emphasized the value of DWI in distinguishing extra-axial epidermoid tumors from arachnoid cysts, showing that epidermoid lesions demonstrate high signal intensity on diffusion-weighted images, unlike arachnoid cysts, which follow cerebrospinal fluid signal characteristics.²⁰ Farhan et al. reported that epidermoid cysts were hyperintense on DWI and had significantly lower ADC values than arachnoid cysts, supporting the diagnostic role of DWI and ADC mapping in this distinction.²¹ In the present study, all arachnoid cysts were markedly hypointense on DWI, whereas all epidermoid cysts were markedly hyperintense, confirming that DWI provides a robust imaging marker for differentiating these two lesions when conventional MRI findings overlap.
The consistent DWI hyperintensity of brain abscesses in our cohort is also in line with the literature. Cervantes-Arslanian et al. demonstrated that brain abscesses typically show marked hyperintensity on DWI, whereas necrotic or cystic tumors may show variable diffusion signal intensity.²² Ashraf et al. reported that DWI increases diagnostic confidence in distinguishing brain abscesses from cystic or necrotic tumors compared with conventional MRI alone.²³ In our study, all abscesses were markedly hyperintense on DWI and hypointense on ADC maps, consistent with restricted diffusion. This pattern likely reflects the high viscosity, cellular debris, inflammatory cells, and proteinaceous content of purulent material within the abscess cavity.
However, our results also showed that DWI signal intensity alone may not always be sufficient to distinguish abscesses from tumors. Although all abscesses were hyperintense on DWI, a considerable proportion of primary tumors and metastases also demonstrated hyperintensity. Specifically, 66.7% of primary tumors and 55.6% of metastases were markedly hyperintense on DWI. Moradi et al. reported that although DWI is helpful in the evaluation of brain abscesses and necrotic tumors, overlap may occur, and additional imaging methods such as MR spectroscopy may improve diagnostic accuracy.²⁴ Lai et al. noted that DWI and ADC measurements are useful but should be interpreted together with conventional MRI findings and clinical context when differentiating abscesses from tumors.²⁵ Our statistical findings support this limitation, as DWI signal intensity was not significantly different between abscesses and primary tumors or between abscesses and metastases.
An important observation in our study was the difference in lesion wall characteristics between abscesses and tumors. While abscess walls were hypointense on both DWI and ADC maps, primary and metastatic tumor walls were more frequently hyperintense on DWI. This finding may be clinically relevant because the lesion wall often represents the most biologically active component in tumors, reflecting cellularity, vascularity, or viable tumor tissue. In contrast, the abscess wall may show different diffusion characteristics from the purulent center. Therefore, evaluating not only the lesion core but also the lesion wall may improve radiological interpretation, particularly in ring-enhancing lesions.
Our findings regarding primary brain tumors are consistent with the known heterogeneity of tumor diffusion patterns. Romano et al. emphasized that DWI in neuro-oncology reflects tumor cellularity, necrosis, edema, and post-treatment changes, but interpretation can be complex because different tumor components may show different diffusion characteristics.¹⁷ In our cohort, primary tumors showed mixed diffusion patterns, with both hypointense and hyperintense lesions. This heterogeneity likely reflects differences in tumor histology, cellular density, necrotic components, hemorrhage, and contrast-enhancing viable tissue. Therefore, DWI should be regarded as a complementary tool rather than a standalone diagnostic method in tumor characterization.
Demyelinating and infectious lesions also showed variable diffusion characteristics. Most demyelinating lesions were hyperintense on DWI, consistent with reports that active inflammatory lesions may exhibit diffusion abnormalities.¹⁴ However, DWI hyperintensity may represent true restriction, T2 shine-through, inflammatory edema, or combined mechanisms; ADC correlation is therefore essential. Herpes encephalitis was hyperintense in all cases, whereas tuberculous meningitis and non-specific viral encephalitis showed mixed patterns. Similar variability has been reported in intracranial tuberculosis¹⁶ and may reflect lesion stage, inflammatory burden, necrosis, and parenchymal involvement.
Demyelinating lesions also showed frequent DWI hyperintensity in our study, with 80% of demyelinating lesions appearing markedly hyperintense. Drake-Pérez et al. described that DWI has several clinical applications in neuroradiology and that diffusion abnormalities may be observed in inflammatory and demyelinating disorders, particularly in active lesions.¹⁴ In the present study, the representative multiple sclerosis plaque demonstrated FLAIR hyperintensity, contrast enhancement, and DWI hyperintensity, compatible with active inflammatory demyelination. However, DWI hyperintensity in demyelinating disease may reflect different mechanisms, including true restricted diffusion, T2 shine-through, inflammatory edema, or a combination of these processes. Therefore, correlation with ADC maps remains essential.
Infectious and encephalitic lesions also showed variable diffusion characteristics. Herpes encephalitis lesions were hyperintense on DWI in all cases, while tuberculous meningitis and non-specific viral encephalitis demonstrated mixed patterns. Parry et al. showed that DWI may provide useful information in intracranial tuberculous lesions, particularly when combined with other MRI techniques such as MR spectroscopy and susceptibility-weighted imaging.¹⁶ In our study, two of three tuberculous meningitis cases showed marked hyperintensity on DWI, while one case was isointense. This variability may reflect differences in lesion stage, inflammatory burden, necrosis, and parenchymal involvement. Thus, DWI can support diagnosis in infectious diseases but should not be interpreted in isolation.
The statistical analysis further highlights the strengths and limitations of DWI. The only statistically significant comparison was between arachnoid and epidermoid cysts, confirming the strong diagnostic value of DWI for this specific differential diagnosis. In contrast, comparisons between abscesses and primary tumors, abscesses and metastases, and primary tumors and metastases were not statistically significant. These results suggest that while DWI is highly reliable for certain cystic lesion distinctions, it has more limited discriminatory power among heterogeneous ring-enhancing or solid-cystic lesions.

Limitations

This study has several limitations. First, the retrospective design may introduce selection bias. Second, the sample size was limited in some lesion subgroups, especially epidermoid cysts, abscesses, bacterial meningitis, SSPE, and glutaric aciduria type 2. Third, DWI and ADC findings were evaluated qualitatively rather than using quantitative ADC measurements. Fourth, histopathological confirmation was not available for all lesion types, particularly benign cystic and infectious lesions. Fifth, imaging was performed using a 1.5 Tesla MRI system and older acquisition protocols; therefore, newer high-resolution DWI techniques, diffusion tensor imaging, or advanced diffusion models may provide additional diagnostic value in contemporary practice. The absence of an a priori sample size calculation, together with the small number of patients in several diagnostic subgroups, may have limited the statistical power of the comparisons and increased the risk of type II error.

Conclusion

In conclusion, DWI provides important complementary information in the evaluation of intracranial non-ischemic lesions. Its greatest diagnostic contribution was observed in differentiating arachnoid cysts from epidermoid cysts and in identifying diffusion restriction within brain abscesses. However, the overlap of DWI signal characteristics among abscesses, primary tumors, and metastases indicates that DWI should be interpreted together with ADC maps, lesion wall characteristics, conventional MRI findings, and clinical data. Assessment of both lesion core and wall diffusion features may improve diagnostic confidence, particularly in ring-enhancing intracranial lesions.

Declarations

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