Magnetic resonance imaging scanning susceptibility weighted imaging sequences in the diagnosis and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy

Abstract

BACKGROUND

Magnetic resonance imaging (MRI) scanning with susceptibility weighted imaging (SWI) sequences plays a significant role in the diagnosis and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy (HIE).

AIM

To observe the role of MRI multi-parameter quantitative indexes in the diagnosis of neonatal HIE.

METHODS

The imaging data from 23 cases of neonatal HIE admitted to the Imaging Department of Ganyu District People's Hospital of Lianyungang City and 23 neonates without HIE admitted during the same period were analyzed retrospectively from August, 2021 to December, 2023. The results of clinical judgment were compared with the results of computed tomography (CT) and MRI examinations.

RESULTS

The degree of cerebral edema (more than moderate), the number of damaged brain regions (> 2), the number of cerebral hemorrhages (> 2), and the percentage of small venous dilatation detected were higher in MRI than in CT examination, and the differences were statistically significant (P < 0.05). The total area of the largest region of cerebral damage and of cerebral hemorrhage observed by MRI examination were significantly larger than those of CT examination (P < 0.01). Multiparametric quantitative MRI combined with diffusion weighted imaging and SWI had higher sensitivity and accuracy than CT diagnosis, and the difference was statistically significant (P < 0.05). The difference in the specificity of the two modes of diagnosis was not significant (P > 0.05).

CONCLUSION

The use of MRI multi-parameter quantitative indexes can accurately diagnose and evaluate neonatal HIE.

Key Words: Hypoxic-ischemic encephalopathy, Neonate, Diagnostic efficacy

Core Tip: Susceptibility weighted imaging (SWI) sequences in magnetic resonance imaging scanning potentially provide richer and more detailed imaging information for neonatal hypoxic-ischemic encephalopathy, facilitating early and accurate diagnosis. In prognostic evaluation, SWI reveals pathological changes related to neurological outcomes, providing essential guidance for clinical decision-making and expectations for patient families. However, interpreting SWI images requires integration with clinical manifestations and other imaging indicators to ensure diagnostic accuracy.

INTRODUCTION

Neonatal hypoxic-ischemic encephalopathy (HIE) refers to brain damage caused by hypoxia and ischemia in the brain of newborns during the perinatal period (including prenatal, perinatal, and early postnatal periods). Neonatal HIE has various etiologies[1-3] that include: (1) Perinatal asphyxia: This is the most common cause, including placental insufficiency, umbilical cord factors (such as, umbilical cord around the neck, prolapse), maternal disease (e.g., hypertension, diabetes mellitus, infection), and intrauterine distress of the fetus; (2) Complications during labor and delivery, such as difficult labor, prolonged labor, obstruction of fetal head descent; and (3) Newborn diseases: Including, severe cardiopulmonary diseases, apnea, severe anemia. Clinical manifestations of HIE include: (1) An altered state of consciousness which can manifest as over-excitement, lethargy, coma and others; (2) Changes in muscle tone: There may be increased muscle tone initially, followed by hypotonia or flaccidity; (3) Convulsions, a common symptom, which may manifest as limb twitching, facial twitching, eye rolling, and others; and (4) Other symptoms such as dyspnea, cyanosis, fluctuation of heart rate and blood pressure, and weakened or absent reflexes.

Neonatal HIE affects the normal bodily functions of newborns and increases the rate of disability and mortality. Newborns with mild disease can recover completely through treatment, whilst those with severe disease can suffer irreversible damage resulting in developmental delays, mental retardation, epilepsy, cerebral palsy, and others[4]. Therefore, early diagnosis of HIE is critical, early detection and treatment can effectively aid children regain neurological function. Recently, diagnostic imaging modalities have been widely used, and spiral computed tomography (CT), magnetic resonance imaging (MRI) and other techniques have gradually become the main diagnostic methods for neonatal HIE. MRI is well-suited to comprehensively obtain neonatal brain images, since it is radiation-free and amenable to multi-sequence and -directional imaging without bone artifacts, which enables the scientific identification and classification of HIE-induced brain damage in infants with increased diagnostic accuracy. Susceptibility weighted imaging (SWI) is an advanced MRI technique with high sensitivity and resolution that aid doctors in identifying and localizing lesions with increased accuracy. For certain conditions, such as cerebral microbleeds, SWI can detect lesions before symptoms appear, which enables early intervention and treatment. By comparing SWI images from different points in time, physicians can assess disease progression and treatment effectiveness. Although SWI is very sensitive, it does not detect all lesions, so a combination of other imaging techniques and clinical information may be needed to make a diagnosis. Overall, SWI sequencing is a powerful neuroimaging tool that can provide important information about brain microstructure, pathological processes, and is valuable in the diagnosis and management of a wide range of neurological disorders.

MATERIALS AND METHODS

General information

The imaging data from 23 cases of neonatal HIE admitted to the Imaging Department of Hanzhong People's Hospital and 23 neonates without HIE examined during the same period were retrospectively analyzed from August, 2017 to December, 2021. There were 25 males and 21 females with gestational weeks ranging from 34-40 wk, with an average of (37.91 ± 2.01) wk, onset time 1-5 min, mean onset time (3.26 ± 0.52) min. Guardians were informed and signed informed consent.

Inclusion criteria: (1) Satisfying the diagnostic criteria for neonatal HIE; (2) History of asphyxia or intrauterine asphyxia; (3) Umbilical artery pH ≤ 7 or an Apgar score of 5 ≤ 5; (4) Developed electrolyte disorders and neurological symptoms after birth; and (5) Complete clinical data including routine MRI, diffusion weighted imaging (DWI) scanning, as well as SWI and CT examinations.

Exclusion criteria: (1) Combined with history of intrauterine infection; (2) Combined with severe renal, cardiac or other organ diseases; (3) Combined with trauma-induced brain injury; and (4) Congenital hereditary diseases.

Methodology

CT examination: A GE 64-row (128-slice) spiral CT (GE Optima CT660) scanner was used. Patients were scanned according to the relevant norms.

MRI: The instrument used was a Signa HDe 1.5T MRI scanner (GE Healthcare, United States) with a GE Advanced Workstation for image processing. Pediatric patients were sedated with a 10% chloral hydrate enema (0.5 mL/kg) 30 min before the MRI procedure. The ears were protected using cotton balls gently plugged into the external ear canal, and the head and other parts of the skull were protected and immobilized using plastic sponges placed on each side of the head to fix the position of the eyebrow arch line. The examination room was well-ventilated and equipped with a professional monitoring system to ensure stable temperature and humidity, as well as suction devices, oxygen bags and nurses. After conventional MRI scanning, DWI, SWI, and other imaging was performed, with specific parameter settings shown in Table 1.

Table 1 Scanning parameters for magnetic resonance imaging examinations.

Imaging format	TR/ms	TE/ms	Field of view (mm)	Layer thickness (mm)
T1WI	2220	22	230 × 230	5
T2WI	640	102	230 × 230	5
FLAIR	7827	170	230 × 230	5
DWI (b = 1000 s/mm2)	4000	94	230 × 230	5
SWI (FA = 15)	49	40	230 × 230	3

T1WI: T1-weighted images; T2WI: T2-weighted images; DWI: Diffusion weighted imaging; SWI: Susceptibility weighted imaging.

Observation indicators

Based on the results of comprehensive clinical judgment, we compared the differences in the imaging indexes of CT and MRI for neonatal HIE, including brain damage, cerebral edema range, number of hemorrhagic foci, and cerebral infarction area, and analyzed the diagnostic efficacy of MRI's multi-parameter quantitative indexes in diagnosing neonatal HIE.

CT and MRI neonatal HIE imaging indexes: Statistics on the degree of cerebral edema, intra-parenchymal hemorrhage, subarachnoid hemorrhage, subventricular hemorrhage, intraventricular hemorrhage, number of cerebral hemorrhages, extent of cerebral damage, total area of the largest region of brain damage, total area of the most hemorrhagic region, number and extent of cerebral infarctions, and dilatation of the small veins in the two modalities of MRI.

Diagnostic efficacy of MRI multi-parameter quantitative index: Sensitivity = true positive/(true positive + false negative) × 100%, specificity = true negative/(false positive + true negative) × 100%, accuracy = (true positive + true negative)/(true positive + false positive + true negative + false negative) × 100%.

Statistical analysis

SPSS 24.0 statistical software was used to analyze the data. Measurement information conforming to a normal distribution was expressed as mean ± SD, and a t-test was used; counting information was expressed as frequency (n) and percentage (%), and χ² test was used, and P < 0.05 was considered as a statistically significant difference.

RESULTS

Comparison of quantitative indicators of the two diagnostic modalities

Based on the results of comprehensive clinical judgment, in 23 cases of neonatal HIE examined using MRI and CT, the degree of cerebral edema (more than moderate), number of brain damaged regions (> 2), number of cerebral hemorrhages (> 2), and percentage of small vein dilatation were higher in MRI and the difference was statistically significant (P < 0.05). Detection of intraventricular hemorrhage, subarachnoid hemorrhage, subventricular hemorrhage, the percentage of intracerebral parenchymal hemorrhage, as well as the number and range of cerebral infarction, were not statistically significant between MRI and CT (P > 0.05) (Table 2).

Table 2 Comparison of the degree of cerebral edema and brain damage between the two modalities, n (%).

Inspection methods	Hydrocephalus (above moderate, n = 20)	Brain damage to brain regions (> 2, n = 22)	Number of cerebral hemorrhages (> 2, n = 17)
MRI	19 (95.00)	21 (95.45)	16 (94.12)
CT	11 (55.00)	14 (63.63)	8 (47.06)
χ2	8.533	6.844	9.067
P value	< 0.05	< 0.05	< 0.05
Inspection methods	Subventricular hemorrhage	Intraventricular hemorrhage	Intracerebral hemorrhage
	(n = 7)	(n = 5)	(n = 10)
MRI	5 (71.43)	4 (80.00)	9 (90.00)
CT	2 (28.577)	3 (60.00)	5 (50.00)
χ2	2.571	0.476	3.809
P value	> 0.05	> 0.05	> 0.05
Inspection methods	Subarachnoid hemorrhage	Number and extent of cerebral infarctions	Small venous dilatation (medicine)
	(Yes, n = 8)	(> 2, n = 7)	(n = 8)
MRI	7 (87.50)	7 (100.00)	8 (100.00)
CT	8 (100.00)	4 (57.14)	1 (12.50)
χ2	1.067	3.818	12.444
P value	> 0.05	> 0.05	< 0.05

MRI: Magnetic resonance imaging; CT: Computed tomography.

In 23 cases of neonatal HIE, the total area of the largest region of brain injury and cerebral hemorrhage detected by MRI were significantly higher than those detected by CT (P < 0.01) (Table 3).

Table 3 Comparison of brain injury and cerebral hemorrhage cut-off area between magnetic resonance imaging and computed tomography scans of neonatal patients with hypoxic-ischemic encephalopathy (mm²).

Inspection method	MRI total area of maximum level of brain damage	Total cerebral hemorrhage in most layers
MRI (n = 23)	14.25 ± 2.31	12.04 ± 1.24
CT (n = 23)	12.14 ± 1.81	10.13 ± 1.02
t	3.448	5.705
P value	0.001	< 0.001

MRI: Magnetic resonance imaging; CT: Computed tomography.

Diagnostic efficacy of neonatal HIE by MRI and CT multi-parameter quantitative indexes

The diagnostic sensitivity of conventional MRI combined with DWI and SWI was higher than that of conventional CT; the difference was statistically significant (P < 0.05). The specificity of MRI with DWI and SWI was not significantly different from that of conventional CT (P > 0.05) (Table 4).

Table 4 Detection of hypoxic-ischemic encephalopathy in newborns by magnetic resonance imaging and computed tomography multi-parameter quantitative indexes.

Methodology	Comprehensive clinical judgment		Sum
	Masculine	Negatives
Routine CT
Masculine	12	3	15
Negatives	11	20	31
Sum	23	23	46
Conventional MRI with DWI and SWI
Masculine	21	2	23
Negatives	2	21	23
Sum	23	23	46

DWI: Diffusion weighted imaging; SWI: Susceptibility weighted imaging; MRI: Magnetic resonance imaging; CT: Computed tomography.

DISCUSSION

HIE poses a significant risk to neonates since it has high rates of mortality and disability, including permanent brain damage with visual and hearing impairment, mental retardation, epilepsy. Early treatment can significantly reduce the damage, facilitate good recovery, and improve patient outcomes. However, due to many limiting factors, the clinical diagnosis of neonatal HIE mainly relies on the clinical history and neurological symptoms of the child. For example, a diagnosis of HIE can be assigned if there is a clear history of abnormal obstetrics, leading to intrauterine distress or if there are clear signs of intrauterine distress, with obvious neurological symptoms lasting for > 24 h, and corresponding imaging indications are observed in the brain[5]. The pathological changes of neonatal HIE include cerebral infarction, cerebral edema, intracranial hemorrhage, and necrosis. As neonatal brain development is incomplete and the body's metabolism, immunity, and other functions are relatively immature, the brain is more susceptible to damage by a variety of factors and the probability of hypoxia, ischemia, and other conditions is increased.

In neonatal brain tissue, the demand for oxygen is high, and the connections of vascular endothelial cells are relatively loose. If hypoxia occurs, there is insufficient oxygen for aerobic metabolism, anaerobic glycolysis is increased, and consequently, ATP decreases sharply. With less ATP, cellular stability is reduced, and metabolites, such as lactic acid, build up, causing dysregulation of the ion pumps and cytotoxic edema[6,7]. The edema is aggravated, cerebral blood flow becomes abnormal, brain cells become necrotic, the venous return is blocked, thus, large concentrations of oxygen free radicals accumulate and damage cell membranes in the brain, leading to impaired integrity of the blood-brain barrier, rupture of blood vessels, and hemorrhage. The persistence of hypoxia reduces the activity of calcium pumps and increases the concentration of calcium ions in the brain, ultimately damaging nerve cells[8]. In a retrospective analysis of 46 neonatal patients (including 23 children with HIE), the degree of cerebral edema (more than moderate), numbers of damaged brain areas (> 2) and cerebral hemorrhages (> 2), and the percentage of small venous dilatation detected in the MRI examination were higher than in the CT examination; and the total areas of the largest region of brain injury and cerebral hemorrhage in the MRI were significantly greater than in the CT examination (P < 0.01). Although spiral CT images readily show areas of hemorrhage, skull base artifacts interfere with the detection of cerebral edema and injury; thus, the diagnostic accuracy needs to be improved. The sensitivity and accuracy of diagnosis using MRI combined with DWI and SWI multi-parameter quantitative index was higher than that of CT diagnosis, and the difference was statistically significant (P < 0.05). Thus, the application of MRI multi-parameter quantitative index is of value for neonatal HIE diagnosis. When neonates experience ischemia and hypoxia, nerve cells are prone to necrosis, and due to incomplete occlusion of blood vessels, reactive congestion occurs after perfusion is restored, resulting in curvilinear high signals such as sheets and dots in the T1-weighted imaging sequence of plasma protein depth. DWI, SWI and other imaging modes can be used to obtain images of the neonatal brain, and accurately understand the blood flow and damage. SWI uses the differences in magnetic susceptibility of tissues in the magnetic field to produce image contrast, and high-resolution three dimensional acquisition imaging to detect the image changes due to the unevenness of the magnetic field including the blood composition and blood flow[9-11], suggesting that applying the MRI multi-parameter quantitative index is more useful than the MRI quantitative index in neonatal HIE diagnosis.

Compared with other MRI sequences, the spatial resolution of SWI may not be optimal, which may limit its ability to identify subtle structural changes. The brain structure and developmental stage of newborns, especially premature infants, can affect the performance of SWI. For example, changes in normal physiological iron deposition may interfere with the interpretation of the disease. Due to neonatal head movement, irregular breathing or breastfeeding, the quality of SWI images may be reduced, and motion artifacts may occur, affecting the accuracy of diagnosis. SWI mainly reflects the difference of magnetic sensitivity between tissues, and its specificity for non-hemorrhagic lesions caused by hypoxia-ischemia (such as simple edema area) is not as good as DWI or apparent diffusion coefficient map. Although SWI can reveal hemorrhagic and iron overload status, its specific quantitative relationship with long-term neurodevelopmental outcomes needs to be evaluated in combination with clinical manifestations and other MRI sequences (such as DWI). In addition, different devices, parameter settings and technical updates may lead to a low degree of standardization of SWI image interpretation.

CONCLUSION

In summary, routine MRI examination combined with DWI, SWI, and other multi-parametric imaging applications is beneficial for the diagnosis of neonatal HIE: MRI scanning SWI sequences can detect the degree of cerebral edema in the neonatal brain, extent of cerebral injury, type and number of cerebral hemorrhages, extent of cerebral infarction, and dilatation of small veins. Therefore, HIE can be accurately diagnosed and evaluated, and a scientific basis can be provided for the subsequent treatment.