# Predictive value of matrix metalloproteinase-9 combined with magnetic resonance spectroscopy for delayed cerebral edema after spontaneous intracerebral hemorrhage

**Authors:** Jing Sun, Lei Chen

PMC · DOI: 10.3389/fphys.2025.1681290 · Frontiers in Physiology · 2026-02-18

## TL;DR

This study shows that combining a blood test for MMP-9 and MRI scans can predict delayed brain swelling after a brain hemorrhage.

## Contribution

The novel contribution is demonstrating that MMP-9 levels and MRS metrics together improve prediction of delayed cerebral edema after intracerebral hemorrhage.

## Key findings

- Higher MMP-9 levels and lower NAA/Cr ratios were independently associated with delayed cerebral edema.
- Combining MMP-9 and MRS metrics improved prediction accuracy with an AUC of 0.874.
- MMP-9 and MRS can guide clinical decisions for patients with spontaneous intracerebral hemorrhage.

## Abstract

The aim of this paper was to evaluate the predictive value of matrix metalloproteinase (MMP)-9 combined with magnetic resonance spectroscopy (MRS) for delayed cerebral edema after spontaneous intracerebral hemorrhage (SICH).

Patients with head computed tomography (CT) suggestive of SICH were retrospectively included. Serum MMP-9 levels were measured within 24 h of the onset of the disease, and MRS was performed on day 3 after admission; N-acetylaspartate/creatine (NAA/Cr) values of edematous areas in MRS were measured and calculated separately. Delayed cerebral edema was defined as a 1-cm increase in the diameter of the peripheral edema around an intracerebral hematoma within 14 days compared with the peripheral diameter of the edema at 7 days, as confirmed by dynamic CT. Demographics of the delayed cerebral edema group were compared with those of the control group, along with baseline clinical data. Multivariate logistic regression analysis was applied to evaluate independent predictors of delayed cerebral edema. The predictive value of MMP-9 and MRS-related indices for delayed cerebral edema was assessed using receiver operating characteristic (ROC) curves.

Eighty SICH patients were included: 27 in the delayed cerebral edema group and 53 in the non-delayed cerebral edema group (control group). Univariate analysis revealed higher MMP-9 levels and NAA/Cr values in the delayed cerebral edema group relative to the control group (both P < 0.05). Multivariate logistic regression analysis disclosed that increased MMP-9 levels (OR = 1.041, 95% CI: 1.019–1.064, P < 0.001) and decreased NAA/Cr values (OR = 0.095, 95% CI: 0.015–0.586, P = 0.011) were independent predictive factors for the development of delayed cerebral edema after SICH. ROC curve analysis reflected that the area under the curve (AUC) of serum MMP-9 and NAA/Cr values alone and the area under the curve of the combination of the two indices for predicting the development of delayed cerebral edema after SICH were 0.835, 0.734, and 0.874, respectively.

The combination of serum MMP-9 detection and MRS has a high efficacy in predicting the occurrence of delayed cerebral edema in SICH, providing guidance for subsequent clinical diagnosis and treatment.

## Linked entities

- **Proteins:** MMP9 (matrix metallopeptidase 9)
- **Chemicals:** N-acetylaspartate (PubChem CID 65065), creatine (PubChem CID 586)

## Full-text entities

- **Genes:** MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}
- **Diseases:** demyelinating diseases (MESH:D003711), consciousness disorders (MESH:D003244), brain injury (MESH:D001930), hypertensive (MESH:D006973), death (MESH:D003643), ICH (MESH:D002543), subarachnoid and epidural hemorrhage (MESH:D013345), brain damage (MESH:D001925), compression (MESH:D009408), pulmonary infection (MESH:D012141), injury (MESH:D014947), Inflammation (MESH:D007249), Hematoma (MESH:D006406), acute cerebral hemorrhage (MESH:D000081032), cerebrovascular-related diseases (MESH:D002561), traumatic brain injury (MESH:D000070642), edema (MESH:D004487), ulcers (MESH:D014456), liver and kidney insufficiency (MESH:D051437), coagulation (MESH:D001778), infection (MESH:D007239), cerebral ischemia (MESH:D002545), neurovascular damage (MESH:D013901), malignant diseases (MESH:D009369), Spontaneous (MESH:D005598), stroke (MESH:D020521), Cerebral edema (MESH:D001929), neuronal damage (MESH:D009410), lymphomas (MESH:D008223), CT (MESH:C000719218), infarction (MESH:D007238), bleeding (MESH:D006470), neurological diseases (MESH:D020271), neurological deterioration (MESH:D009422), Coma (MESH:D003128), cognitive impairment (MESH:D003072), brain tumors (MESH:D001932), neurological deficits (MESH:D009461), necrosis (MESH:D009336)
- **Chemicals:** zinc (MESH:D015032), Cr (MESH:D003401), Cr (MESH:D002857), N-acetylaspartate (MESH:C000179), glutamine (MESH:D005973), glucose (MESH:D005947), glutamate (MESH:D018698)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956724/full.md

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Source: https://tomesphere.com/paper/PMC12956724