1. Introduction

Today, acute ischemic stroke remains one of the foremost causes of mortality and long-term disability worldwide, affecting approximately 15 million individuals annually, according to epidemiological data from the World Health Organization. The complex pathophysiology of cerebral ischemia necessitates advanced diagnostic methods capable of accurately characterizing the metabolic consequences of diminished cerebral perfusion and identifying salvageable brain tissue amenable to therapeutic intervention. While conventional neuroimaging techniques remain indispensable, they often lack the sensitivity required to detect the earliest biochemical alterations that occur within minutes of stroke onset, thereby creating a critical diagnostic window that may influence clinical outcomes. The emergence of magnetic resonance spectroscopy as a diagnostic modality has significantly transformed the evaluation of cerebral metabolism in stroke patients. By non-invasively assessing key metabolic biomarkers such as N-acetylaspartate and lactate, this technique offers unique insight into cellular bioenergetics and neuronal viability during the acute phase of ischemia, thus equipping clinicians with a robust tool for early detection and prognostic evaluation. [6, 112-113] The clinical utility of magnetic resonance spectroscopy extends beyond diagnosis, offering valuable information for therapeutic monitoring and outcome prediction. Proton and phosphorus-based spectroscopic analyses enable detailed assessment of metabolic activity and metabolite concentrations in affected brain regions, helping to determine tissue viability and the likelihood of functional recovery. This metabolic profiling is especially critical during the hyperacute phase of stroke, when timely interventions such as thrombolysis or neuroprotective therapies can yield the greatest benefit. [1, 45-46]

The integration of magnetic resonance spectroscopy with traditional imaging modalities has fostered a comprehensive, multimodal approach to stroke diagnosis. Combined with structural and perfusion magnetic resonance imaging, spectroscopy contributes a metabolic perspective that enhances diagnostic precision and supports more informed decisions regarding treatment eligibility and therapeutic timing. This synergistic approach addresses the inherent limitations of individual imaging techniques and strengthens clinical decision-making in the acute care setting. Recent technological advances have further improved the feasibility and clinical implementation of magnetic resonance spectroscopy in acute stroke evaluation. Innovations such as rapid acquisition protocols including six-minute multimodal imaging protocols have significantly reduced scan times, making spectroscopic assessment more accessible in emergency contexts and mitigating concerns about prolonged evaluations in critically ill patients. As a result, magnetic resonance spectroscopy has become a practical and integral component of modern acute stroke diagnostic pathways.

2. Materials and Methods

The application of magnetic resonance spectroscopy to acute ischemic stroke is fundamentally based on the understanding of cellular metabolic changes that occur during cerebral ischemia. When cerebral blood flow is reduced below critical thresholds, typically less than 20 milliliters per 100 grams of tissue per minute, a cascade of metabolic events is initiated that can be detected and quantified through spectroscopic analysis. [5, 17-18] The primary metabolic consequence of reduced oxygen and glucose delivery to brain tissue is the shift from aerobic to anaerobic metabolism, resulting in characteristic changes in key neurometabolites that serve as sensitive indicators of tissue status. N-acetylaspartate, considered the most reliable marker of neuronal integrity and mitochondrial function, demonstrates rapid and progressive decline during cerebral ischemia. This amino acid derivative, which is synthesized exclusively in neurons and their processes, serves as a metabolic marker of neuronal density and viability. The reduction in N-acetylaspartate in visible infarcts has been directly related to the reduction in blood flow to the affected tissue, which correlates with infarct extent and clinical outcome. The spectroscopic quantification of N-acetylaspartate provides clinicians with a non-invasive method to assess neuronal loss and predict functional recovery potential. Lactate accumulation represents another critical metabolic marker detectable through magnetic resonance spectroscopy during acute stroke. [3, 28] The elevation of lactate levels reflects the activation of anaerobic glycolysis in response to reduced oxygen availability, serving as an indicator of tissue hypoxia and metabolic stress. The presence of lactate in stroke patients, along with N-acetylaspartate changes, provides valuable information about the time course of metabolic dysfunction and its relationship to clinical presentation. The spectroscopic detection of lactate can occur within hours of stroke onset, often preceding the appearance of conventional magnetic resonance imaging abnormalities. The creatine and phosphocreatine system, which plays a crucial role in cellular energy metabolism, also undergoes significant alterations during cerebral ischemia. Total creatine levels, typically used as an internal reference standard in spectroscopic studies, may remain relatively stable in the acute phase but can show changes in chronic stroke conditions. The ratio of metabolites to creatine provides normalized measurements that account for technical variations and enhance the reliability of spectroscopic assessments. Choline-containing compounds, including phosphocholine and glycerophosphocholine, reflect membrane turnover and cellular integrity. Elevated choline levels may indicate membrane breakdown and cellular damage, while decreased levels can suggest reduced cellular density. The spectroscopic analysis of choline compounds provides additional information about the cellular consequences of ischemia and the potential for tissue recovery.

The clinical use of magnetic resonance spectroscopy in acute stroke care offers several crucial benefits that significantly influence diagnosis and treatment outcomes. Its foremost application is the early detection of metabolic changes that occur before abnormalities become visible on standard neuroimaging, enabling timely therapeutic intervention within the optimal treatment window. The high sensitivity and specificity of spectroscopy also aid in distinguishing acute ischemic stroke from stroke mimics, a common diagnostic challenge in emergency care. Spectroscopy plays an important role in prognostic evaluation by linking metabolite changes within the infarcted area to clinical outcomes. This allows for more accurate patient counseling and the development of tailored rehabilitation strategies based on the likelihood of functional recovery. Another valuable application is therapeutic monitoring. Spectroscopy enables real-time tracking of metabolic responses to treatments such as thrombolysis, neuroprotective therapy, and thrombectomy. These insights help clinicians assess treatment efficacy and adjust interventions as needed. Beyond acute care, magnetic resonance spectroscopy is useful for detecting early neurodegenerative changes associated with post-stroke cognitive impairment. This expands its role to predicting long-term neurological outcomes and planning appropriate follow-up care. When combined with diffusion-weighted and perfusion magnetic resonance imaging, spectroscopy contributes to a multimodal diagnostic approach. This integrated strategy provides a more complete understanding of stroke pathophysiology and supports more precise and personalized treatment decisions.

Advancements in magnetic resonance spectroscopy technology have greatly improved its clinical use in acute stroke care. Modern systems now utilize advanced pulse sequences, enhanced magnetic field homogeneity techniques (shimming), and refined data processing algorithms that allow for the rapid acquisition of high-quality spectra, even in emergency conditions. The introduction of single-voxel and multi-voxel methods enables simultaneous assessment of multiple brain regions, supporting a more comprehensive metabolic evaluation of ischemic tissue. Innovative developments, such as the measurement of brain temperature using magnetic resonance spectroscopy, provide additional physiological insights into acute stroke pathology. Elevated temperatures in ischemic areas, often caused by reduced cerebral perfusion and early inflammatory responses, can now be detected and quantified, adding a valuable layer to metabolic assessment. Despite technological progress, quality assurance and standardization remain vital. Variations in magnetic field strength, acquisition settings, and processing techniques can influence the accuracy of spectroscopic findings. Thus, the implementation of standardized protocols and robust quality control is essential to ensure consistency and reliability across different clinical environments. To accommodate the urgency of acute stroke cases, acquisition protocols have been optimized for speed and patient comfort. The development of rapid multimodal magnetic resonance imaging workflows, including spectroscopy, that can be completed in under six minutes has made this technique practical and efficient for emergency stroke evaluation. [7, 89]

The quantitative analysis of metabolic biomarkers via magnetic resonance spectroscopy offers objective indicators of tissue viability and prognosis in patients with acute ischemic stroke. Key metabolites such as N-acetylaspartate, lactate, creatine, and choline compounds serve as critical markers of neuronal function, energy metabolism, and cellular integrity. N-acetylaspartate is widely regarded as a reliable marker of neuronal viability and mitochondrial health. Its concentration in healthy brain tissue ranges between 8 and 12 millimoles per kilogram, and a marked reduction is typically observed in ischemic regions. [2, 34] This decrease correlates with the extent of neuronal damage and is predictive of potential functional recovery. Lactate, a byproduct of anaerobic glycolysis, rises sharply in response to hypoxia. While normally present at concentrations below 1 millimole per kilogram, lactate levels increase significantly during ischemia. Its characteristic doublet signal at 1.3 parts per million on magnetic resonance spectroscopy serves as a robust indicator of metabolic stress. Creatine and phosphocreatine constitute the creatine energy system, essential for maintaining cellular energy homeostasis. In the acute stroke setting, total creatine levels tend to remain stable, making creatine a useful reference metabolite for normalization. [4, 30] Nonetheless, changes in the creatine-to-phosphocreatine ratio can reflect alterations in energy metabolism and cellular stress. Choline-containing compounds, including phosphocholine and glycerophosphocholine, are indicators of membrane turnover. Elevated choline levels may signal cell membrane disruption, while reduced levels may suggest diminished cell density. The choline-to-creatine ratio provides a standardized measure of membrane metabolism, useful for assessing the extent of structural damage in ischemic brain regions.

3. Result and Discussion

The therapeutic implications of magnetic resonance spectroscopy in acute stroke care extend beyond diagnosis to encompass treatment selection, monitoring, and outcome prediction. The metabolic information provided by spectroscopy enables clinicians to make more informed decisions about therapeutic interventions, including thrombolysis, neuroprotection, and mechanical thrombectomy. By identifying tissue at risk and assessing metabolic viability, spectroscopy can help optimize treatment strategies and improve patient outcomes. The role of spectroscopy in neuroprotection research has gained increasing attention as investigators seek to develop effective treatments for acute stroke. The ability to monitor metabolic changes in real-time provides valuable insights into the mechanisms of neuroprotective agents and their effects on cellular metabolism. This information is crucial for the development and optimization of therapeutic interventions that can preserve neuronal function and improve recovery. Treatment monitoring through serial spectroscopic examinations enables clinicians to assess the effectiveness of therapeutic interventions and adjust treatment strategies accordingly. Changes in metabolite concentrations over time can indicate treatment response and guide decisions about continued therapy or alternative approaches. This dynamic monitoring capability represents a significant advantage of spectroscopy over static imaging techniques. The prediction of clinical outcomes based on spectroscopic findings has important implications for patient management and resource allocation. By identifying patients who are likely to have good functional recovery, clinicians can focus intensive rehabilitation efforts on those most likely to benefit. Conversely, the identification of patients with poor prognosis can guide discussions about care goals and treatment limitations.

The future of magnetic resonance spectroscopy in acute stroke care involves continued technological advancement and expanded clinical applications. Emerging techniques such as magnetic resonance spectroscopic imaging and multi-nuclear spectroscopy promise to provide even more detailed metabolic information about stroke-affected brain tissue. The development of portable and point-of-care spectroscopic systems could revolutionize acute stroke care by enabling metabolic assessment in ambulatory and emergency settings. The integration of spectroscopic data with artificial intelligence and machine learning algorithms represents a promising avenue for improving diagnostic accuracy and outcome prediction. Advanced computational approaches can analyze complex spectroscopic patterns and identify subtle metabolic changes that may not be apparent through conventional analysis methods. The standardization of spectroscopic protocols and the establishment of normative databases are essential for the widespread clinical adoption of magnetic resonance spectroscopy in stroke care. Collaborative efforts between clinical centers and research institutions will be crucial for developing evidence-based guidelines and best practices for spectroscopic assessment of stroke patients. The expansion of spectroscopic applications to include assessment of cognitive function, neuroplasticity, and recovery mechanisms represents an exciting frontier in stroke research. By providing insights into the metabolic basis of neurological recovery, spectroscopy can inform the development of targeted rehabilitation strategies and therapeutic interventions.

Despite its significant clinical potential, magnetic resonance spectroscopy faces several limitations and challenges that must be addressed for optimal clinical implementation. Technical challenges include susceptibility to motion artifacts, magnetic field inhomogeneity, and signal contamination from cerebrospinal fluid and surrounding tissues. These factors can compromise spectroscopic quality and limit the reliability of metabolic measurements, particularly in critically ill stroke patients. The interpretation of spectroscopic data requires specialized expertise and training, which may limit its widespread adoption in clinical practice. The complexity of spectroscopic analysis and the need for quality control measures represent significant barriers to implementation in routine clinical settings. Educational initiatives and training programs are essential for developing the necessary expertise among clinicians and technologists. Patient selection and contraindications for spectroscopic examination must be carefully considered in acute stroke care. Factors such as patient stability, ability to remain motionless during examination, and presence of contraindications to magnetic resonance imaging can limit the applicability of spectroscopy in certain clinical scenarios. The development of rapid acquisition protocols and motion-resistant techniques can help address some of these limitations. The cost-effectiveness of magnetic resonance spectroscopy in acute stroke care requires careful evaluation, particularly in resource-limited settings. The additional time, equipment, and expertise required for spectroscopic assessment must be weighed against the potential clinical benefits and improved patient outcomes. Economic analyses and cost-effectiveness studies will be important for informing healthcare policy and resource allocation decisions.

In summary, magnetic resonance spectroscopy has become an essential tool in the diagnosis and management of acute ischemic stroke, offering precise insights into cerebral metabolism and neuronal viability. By enabling the early detection of key metabolic biomarkers, it allows clinicians to assess tissue status, guide therapeutic decisions, and predict clinical outcomes with greater accuracy than conventional imaging. Its integration into multimodal imaging enhances diagnostic precision across all stages of stroke care, from early detection to outcome monitoring. Technological advancements, including rapid acquisition protocols and standardized methodologies, have improved its clinical feasibility and reliability.

4. Conclusions

As treatment strategies evolve, the ability of magnetic resonance spectroscopy to support personalized, metabolism-based interventions highlights its growing therapeutic value. Future innovations, such as artificial intelligence-assisted analysis and portable systems, are expected to further expand its role in precision stroke care and long-term neurological assessment. Magnetic resonance spectroscopy stands as a cornerstone in modern stroke diagnostics, offering powerful metabolic insights that can significantly improve patient outcomes.