European Journal of Cardiovascular Medicine

Ischemic stroke remains a major cause of morbidity and mortality worldwide. Rapid and accurate diagnosis of stroke onset is essential to enable time-critical interventions such as thrombolysis and mechanical thrombectomy[1]. However, clinical estimation of infarct age is often difficult. Magnetic resonance imaging (MRI), particularly diffusion-weighted imaging (DWI), has emerged as the most sensitive modality for detecting early ischemic changes[2].

DWI abnormalities appear within minutes of arterial occlusion due to cytotoxic edema. The restricted diffusion of intracellular water results in hyperintensity on DWI and a marked decrease in Apparent Diffusion Coefficient (ADC). Over time, ADC evolution reflects the underlying pathophysiological changes, including membrane failure, vasogenic edema, liquefactive necrosis, and gliosis[3].

Prior literature demonstrates a characteristic temporal ADC pattern:

• Lowered ADC within minutes to hours (hyperacute/acute phase)
• Pseudonormalization around day 7–10
• ADC elevation beyond normal values in chronic infarction

Despite multiple studies, discrepancies persist regarding the precise timeline of ADC normalization and elevation[4]. Understanding the temporal pattern of ADC changes is essential for infarct age estimation, treatment selection, and prognostication.

This study investigates temporal ADC variations in ischemic stroke over a defined timeline using relative ADC (rADC) values, which minimize inter-patient physiological variability.

AIMS AND OBJECTIVES

To assess the temporal variation of apparent diffusion coefficient (ADC) values in ischemic stroke patients and correlate these values with infarct duration.

This retrospective observational study was conducted in the Department of Radiodiagnosis at Nandha Medical College and Hospital, Erode, Tamil Nadu, over a period of 12 months. A total of 100 consecutive patients with MRI-confirmed ischemic stroke were included in the study.

MRI Protocol

All MRI examinations were performed using a 1.5T Siemens Magnetom Essenza scanner. The imaging protocol included standard sequences such as T1-weighted imaging, T2-weighted imaging, and FLAIR, along with diffusion-weighted imaging (DWI) acquired at b-values of 0 and 1000 s/mm². Corresponding Apparent Diffusion Coefficient (ADC) maps were automatically generated by the system for quantitative analysis.

ROI Selection

For quantitative analysis, two regions of interest (ROIs) were placed within each infarct—one at the center and the other at the periphery—and the corresponding ADC values were averaged to obtain the mean infarct ADC. A reference ROI was positioned in the contralateral normal-appearing brain parenchyma to calculate the relative ADC (rADC), defined as (infarct ADC / contralateral ADC) × 100%. Care was taken to place all ROIs at least 2–3 pixels away from cerebrospinal fluid (CSF) spaces to avoid artificially elevated ADC values

Inclusion & Exclusion Criteria

The study included patients of any age or sex who presented with clinical suspicion of ischemic stroke and had the diagnosis confirmed on MRI. Patients were excluded if they demonstrated hemorrhagic transformation, had neoplastic or infective intracranial lesions, or sustained post-traumatic brain injury. Cases with poor image quality that interfered with accurate ADC measurement were also excluded from the analysis

Grouping Based on Time from Onset

Statistical Analysis

Statistical analysis was performed using SPSS version 25. Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were summarized as frequencies and percentages. Differences in rADC values across the eight time groups were evaluated using one-way ANOVA, and the relationship between ADC values and infarct duration was assessed using Pearson’s correlation. Linear regression analysis was conducted to model the predictive association between infarct age and rADC. Diagnostic performance was further evaluated using Receiver Operating Characteristic (ROC) curve analysis. A p-value of <0.05 was considered statistically significant

The demographic characteristics of the study population are summarized in Table 1& figure 1, which shows that among the 100 ischemic stroke patients included in the study, males constituted 58% and females 42%, reflecting a male predominance in stroke incidence. Patient presentation times varied considerably, with the majority (43%) arriving within the first 24 hours of symptom onset. As detailed in Table 2& figure 2, 14% of patients presented within 0–6 hours (Group A), while 29% presented between 6–24 hours (Group B). A further 26% were imaged between 24 hours and 3 days (Group C), followed by progressively fewer patients in later stages, underscoring the predominance of early presentations in the cohort.

TABLE 1. Demographic Characteristics of the Study Population

TABLE 2. Distribution of Patients Based on Time From Symptom Onset

A clear and progressive temporal variation in relative ADC (rADC) values was observed across the eight time groups (Table 3& figure 3). The rADC was lowest in hyperacute infarcts (41% in Group A), increased modestly through the late hyperacute and acute periods (58% in Group B and 66% in Group C), and rose substantially during the subacute phase, reaching 108% by days 7–10 (Group E). The highest rADC values were seen in chronic infarcts (>21 days), reaching 221% (Group H). This pattern aligns precisely with the expected physiological evolution of ischemic tissue, as summarized in Table 4& figure 4, where stroke phases are mapped to their corresponding time groups. The gradual rise from cytotoxic edema–related restricted diffusion in early phases to vasogenic edema and eventual tissue liquefaction in chronic stages is clearly reflected in the rADC trajectory.

TABLE 3. Temporal Variation of Relative ADC (rADC) Values

TABLE 4. Mapping Time Groups to Stroke Phases

TABLE 5. Summary of Statistical Analysis

TABLE 6. Representative Case Data

Statistical analyses, summarized in Table 5, further reinforce the robustness of these temporal changes. A significant difference in rADC values across the eight groups was demonstrated by one-way ANOVA (F = 45.76, p < 0.001), and post-hoc Tukey testing confirmed significant pairwise differences. Pearson’s correlation analysis revealed a strong positive correlation between infarct duration and rADC (r = 0.89, p < 0.001), indicating that rADC reliably increases with time from symptom onset. Linear regression yielded the predictive model ADC (%) = 32.5 + 8.6 × (Days), with an R² of 0.79, showing that nearly 80% of the variability in ADC values is explained by infarct age. Diagnostic performance analysis using ROC curves demonstrated excellent classification accuracy (AUC = 0.94), with high sensitivity (91.2%) and specificity (88.7%) for differentiating early from late infarcts.

Representative cases illustrating these findings are shown in Table 6, which highlights typical ADC behavior in acute, subacute, and chronic infarcts. In acute infarction, ADC values were markedly reduced (e.g., 357 × 10⁻⁶ mm²/s with rADC 47%), reflecting restricted diffusion due to cytotoxic edema. Subacute infarcts demonstrated pseudonormal or slightly elevated ADC values (898 × 10⁻⁶ mm²/s; rADC 108%), consistent with evolving edema and membrane breakdown. Chronic infarcts exhibited markedly elevated ADC values (2719 × 10⁻⁶ mm²/s; rADC 375%), reflecting liquefaction and gliotic transformation.

This study clearly demonstrates the classical temporal evolution of Apparent Diffusion Coefficient (ADC) values following ischemic stroke, reflecting the dynamic cellular and extracellular changes that occur as infarction progresses[6-7]. In the hyperacute and acute phases (0–7 days), ADC values were markedly reduced, ranging from 41% to 86%, which corresponds to the predominance of cytotoxic edema. During this period, failure of ATP-dependent ion pumps results in intracellular sodium and water accumulation, leading to cellular swelling and restricted Brownian motion of water molecules, thus reducing ADC values—a well-established hallmark of early ischemia as described in prior diffusion imaging studies [8-9]. As the infarct transitions into the subacute phase (7–21 days), ADC values progressively increased (108–176%), reflecting a shift from cytotoxic to vasogenic edema. This rise is attributed to the breakdown of cell membranes, increased extracellular water content, and disruption of the blood–brain barrier, permitting freer diffusion of water molecules within the extracellular space [10]. In the chronic phase (>21 days), ADC values reached their highest levels (approximately 221%), which is consistent with tissue liquefactive necrosis, encephalomalacia, and eventual replacement of necrotic brain parenchyma by cerebrospinal fluid—a medium with inherently high diffusivity [11].

An important observation in this study is the pseudonormalization of ADC values observed around 7–10 days post-stroke, wherein ADC values briefly approximate those of normal brain tissue before rising in later stages. This phenomenon, widely reported in diffusion imaging literature, represents the equilibrium phase during the transition from cytotoxic edema in the early stage to vasogenic mechanisms in the later stage [12]. Recognition of this transient pseudonormal window is essential, as misinterpretation may lead to underestimation of infarct age if radiologists rely solely on ADC maps without considering clinical context and complementary imaging sequences.

The clinical implications of these findings are significant. Temporal ADC patterns serve as valuable biomarkers for estimating the age of an infarct, particularly when the exact onset of symptoms is unknown—a common challenge in emergency stroke evaluation. Accurate estimation of stroke age is crucial for determining eligibility for reperfusion therapies such as intravenous thrombolysis and mechanical thrombectomy, which are highly time-dependent interventions [13-14]. Furthermore, rising ADC values in the subacute and chronic stages help in assessing tissue viability, anticipating infarct maturation, and guiding decisions regarding rehabilitation and long-term prognosis. In medicolegal contexts, where precise timing of neurological injury may be required, ADC evolution offers objective radiological evidence to support clinical judgment. Overall, the temporal progression of ADC values observed in this study strongly aligns with established pathophysiological models and reinforces the indispensable role of diffusion-weighted MRI in the comprehensive evaluation and management of ischemic stroke

Apparent Diffusion Coefficient values vary predictably with stroke evolution and offer a reliable indicator of infarct age. DWI combined with ADC mapping significantly enhances early detection, clinical staging, and prognostication in ischemic stroke. Its utility is greatest in the hyperacute phase, where timely intervention can dramatically improve outcomes.

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