|Year : 2017 | Volume
| Issue : 2 | Page : 67-75
Role of magnetic resonance imaging in biometric evaluation of corpus callosum in hypoxic ischemic encephalopathy patients
Amit Garhwal, Ashwin S Patil
Department of Radiodiagnosis, J N Medical College, KLE University, Belagavi, Karnataka, India
|Date of Web Publication||11-Oct-2017|
Department of Radiodiagnosis, J N Medical College, Belagavi - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Corpus callosum (CC) has an important role in establishing hemispheric lateralization of function. Significance of this structure which is the primary white matter commissure of the brain lies in the fact that damage to the CC during development has been found to be associated with poor neurological outcome and neuropsychological performance. Magnetic resonance imaging (MRI) can precisely detect, localize, and evaluate damage to CC in hypoxic-ischemic encephalopathy (HIE) patients and assist in reaching to at an accurate anatomical diagnosis, thus heeling in further management of the patient. Objectives: The objective of this study is to analyze the effect of HIE on CC morphometry by assessing various diameters of CC. Materials and Methods: Fifty-four patients with history of hypoxic-ischemic injury referred to the Department of Radiodiagnosis were included in the study. All the patients were made to undergo MRI of the brain using Siemens Symphony Magnetom 1.5 Tesla scanner after taking informed consent for the same. The findings of MRI brain were assessed and analyzed. Data analysis was done using percentages of different diagnosis and outcomes made by MRI brain were computed and compiled. Results: In the present study, male predominance is seen, 77.78% patients were male and 22.22% were female. In the present study, maximum numbers of patients were <1 year of age (37.04%). In the present study, we see that the isthmus was the most commonly affected portion of CC. Children who did not cry at birth, born with low birth weight, low Apgar score were positively correlated with severity of damage to CC. Conclusion: From the present study, it was noted that MRI is very efficient tool in evaluating morphometry of CC in HIE. Its noninvasiveness and no exposure to ionizing radiation is an added advantage. However, experience and understanding of the principles are essential for accurate diagnosis.
Keywords: Corpus callosum, hypoxic ischemic injury, magnetic resonance imaging
|How to cite this article:|
Garhwal A, Patil AS. Role of magnetic resonance imaging in biometric evaluation of corpus callosum in hypoxic ischemic encephalopathy patients. J Sci Soc 2017;44:67-75
|How to cite this URL:|
Garhwal A, Patil AS. Role of magnetic resonance imaging in biometric evaluation of corpus callosum in hypoxic ischemic encephalopathy patients. J Sci Soc [serial online] 2017 [cited 2018 Dec 9];44:67-75. Available from: http://www.jscisociety.com/text.asp?2017/44/2/67/216496
| Introduction|| |
Birth asphyxia, more appropriately called hypoxic-ischemic encephalopathy (HIE) remains one of the major causes of mortality and morbidity in neonates. There is no gold standard test for HIE-fetal distress, acidemia, Apgar score, and other clinical markers of possible intrapartum injury have low-positive predictive value. Brain hypoxia and ischemia due to systemic hypoxemia, reduced cerebral blood flow (CBF), or both are the primary physiological processes that lead to HIE.,,
Neonatal encephalopathy may result from hypoxic-ischemic injury (by far the most common cause), infectious diseases, metabolic disorders, trauma, and congenital disorders. The term hypoxic-ischemic injury is used to designate any brain impairment caused by insufficient oxygenation and blood flow. This term should not be confused with HIE, a condition that is diagnosed on the basis of specific clinical findings of profound acidosis, a poor Apgar score (0–3) at birth, seizure, coma, hypotonia, and multiorgan dysfunction.
Neonatal HIE occurs in one to six per 1000 live full-term births. Of affected newborns, 15%–20% of affected newborns will die in the postnatal period, and an additional 25% will sustain childhood disabilities., The presence of an abnormal neurologic examination in the first few days of life is the single most useful indicator that a brain insult has occurred. Neonates with mild encephalopathy do not have an increased risk of motor or cognitive deficits. Neonates with severe encephalopathy have an increased risk of death and an increased risk of cerebral palsy (CP) and mental retardation amongst survivors.,
There is no consensus regarding the gestational age demarcation at which an infant is considered preterm or term. However, most authors describe a pattern of injury in neonates who are <36 weeks gestation that is distinct from the pattern in neonates 36 weeks or older.,, Thus, for the purpose of this discussion, it is reasonable to designate a preterm neonate as being one who is <36 weeks gestation.
Accurate identification and characterization of the severity, extent, and location of brain injury rely on the selection of appropriate neuroimaging modalities, including ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI). Encephalopathy due to hypoxic-ischemic injury usually manifests within the first few hours after birth. US used to be the first-line imaging technique for the evaluation of the newborn brain. Since the last few years we are witnessing a trend toward increasing role of MRI in the investigation of HIE because of greater sensitivity and specificity. Newer diagnostic techniques such as diffusion-weighted MRI and magnetic resonance (MR) spectroscopy provide further insight into HIE and the potential for possible therapeutic intervention.
Among myriad manifestations of HIE, one of the most obvious brain abnormalities in individuals born very preterm is thinning of the corpus callosum (CC). Advancements in the field of MRI have truly enabled the diagnostic assessment of CC. Such injury may be partly explained by the vulnerability of the developing CC to hypoxic-ischemic damage and hemorrhage, possibly due to the intrinsic vulnerability of immature oligodendrocytes. Studies of patients with agenesis of the CC or commissurotomy have demonstrated that the CC plays an important role in establishing hemispheric lateralization of function. The significance of this structure which is the primary white matter commissure of the brain lies in the fact that damage to the CC during development has been found to be associated with poor neurological outcome and neuropsychological performance.
The data of biometry of CC in HIE patients is scarcely available. Hence, this study is an effort toward drawing a conclusion about the growth pattern of CC in such patients. CC has been measured on mid-sagittal MRI in HIE patients as in the previous studies. Using quantitative methods, the present study focused on the mid-sagittal MR measurement of the CC in HIE patients. The primary objective was to observe the changes in the dimensions of the CC among HIE patients.
| Materials and Methods|| |
This is a cross-sectional study.
Duration of study
The study was carried out on 54 patients from January 2015 to December 2015 and fulfilling the inclusion and exclusion criterion.
A total of 54 patients were included in the study. All the patients were clinically proven cases of HIE. The changes in corpus callosal morphometry were studied.
- Age group <18 years
- Patients with clinically proven HIE.
- Age more than18 years
- Uncooperative patients (due to claustrophobia or loud noise of the MRI machine)
- Noncompatible metal implant or prior injuries from metal objects.
Concurrence was taken from the chairman and academic, scientific, and ethical committees for the study. Informed consent was taken from the patient and/or guardian for the MRI scans.
The study was carried out on T1 mid-sagittal sections of the brain for morphometric analysis of CC in 54 patients of birth asphyxia history. Morphometric analysis of the corpus callosal dimensions of the patients was made on available mid-sagittal T1-weighted images at the level of cerebral aqueduct in hospital's picture archiving and communication system (PACS).
All the MRI scans were done using Siemens MAGNETOM Symphony 1.5T using the head coils. Patients were made to lie supine in the magnet during the procedure. The protocol included acquisition of spin echo images with parameters of 529/9.7/1 (repetition time/echo time/excitations), 5 mm contiguous axial sections, a matrix of 256 × 256, and a field of view of 230 mm.
Based on Garel et al. methodology, CC was calculated on mid-sagittal T1-weighted image by following methods:
- Measurement of the anteroposterior diameter (APD) of the CC, the distance between the anterior aspect of the genu and the posterior aspect of the splenium
- Measurement of the true length of CC (LCC), the curvilinear distance between the rostrum and the splenium at mid-thickness of the CC
- Measurement of the thickness of the CC, at the level of the genu (GT), body (BT), isthmus (IT), and splenium (ST)
- Measurement of the IT when the isthmus could not be identified because of insufficient CC modeling. IT was measured at the level where the fornix abuts the CC (CC-fornix junction)
- Measurement of the fronto-occipital diameter (FOD), the distance between the extreme points of the frontal and occipital lobes [Figure 1].
|Figure 1: Description of the different biometric parameters measured with magnetic resonance imaging. (a) Measurement of the anteroposterior diameter of the corpus callosum, the distance between the anterior aspect of the genu and the posterior aspect of the splenium. (b) Measurement of the true length of corpus callosum, the curvilinear distance between the rostrum and the splenium at midthickness of the corpus callosum. (c) Measurement of the thickness of the corpus callosum, at the level of the genu, body, isthmus, and splenium. (d) Measurement of the isthmus thickness when the isthmus could not be identified because of insufficient corpus callosum modeling. Isthmus thickness was measured at the level where the fornix abuts the corpus callosum (corpus callosum - fornix junction). (e) Measurement of the fronto-occipital diameter, the distance between the extreme points of the frontal and occipital lobes. (f) Evaluation of the position of the splenium. A line was drawn along the dorsal surface of the brain stem. Another line was drawn parallel to the first one and passing at the level of the most posterior point of the splenium. The S/T distance between those lines was measured at the level of the fastigium|
Click here to view
The categorical data were expressed as rates, ratios, proportions, and percentages.
| Results|| |
The present 1-year cross-sectional study was carried out from January 2015 to December 2015. A total of 54 patients who fulfilled the selection criteria during the study were enrolled.
The data were analyzed, and the final observations were tabulated as below.
In this study, the maximum number of patients were in the age group of <1 year which were 37.04% (n = 20) of total followed by age Group 1–2 years having 25.93% (n = 14) in this group. The mean age was 3.05 ± 3.87 years [Table 1] and [Graph 1].
In our study, the majority of the patients were male comprising 75% of males, who comes in under one-year age group followed by females comprising 25% of total females. These too come in <1 year age group [Table 2] and [Graph 2].
|Table 2: Distribution of the number of children as a function of age and sex|
Click here to view
In the present study, majority were male 77.78% (n = 42). The male to female ratio was 3.5:1[Table 3] and [Graph 3].
In the present study, maximum patients were born preterm comprising 77.78% of total. Among these, 76.19% were male, and 23.81% were female. P =0.89 so the difference of gender in preterm and term patients is statistically insignificant [Table 4] and [Graph 4].
|Table 4: Distribution of the number of children as a function of birth history and sex|
Click here to view
In our study, 77.78% patients were having history of Neonatal Intensive Care Unit (NICU) stay among which majority were male patients 73.81% of total followed by 26.19% female patients. As the P = 0.35 so it's statistically insignificant [Table 5] and [Graph 5].
|Table 5: Distribution of the number of children by Neonatal Intensive Care Unit stay and sex|
Click here to view
In our study, maximum patients, i.e., 55.56% (n = 30) were having Apgar score of 2. Among which majority were males comprising 83.33% (n = 25) P = 0.515. There is statistically insignificant difference (P > 0.05) among various groups with different Apgar scores as suggested by Chi-square test [Table 6] and [Graph 6].
In the present study, the majority of patients did not cry at birth 75.93% (n = 41). Among which, maximum were male 82.93% (n = 34). The difference of gender among groups is statistically insignificant as the P = 0.2172 (>0.05) [Table 7] and [Graph 7].
In the present study, majority of the patients were having history of low birth weight 70.37% (n = 38), out of which 78.95%, i.e., (n = 30) were male child [Table 8] and [Graph 8].
|Table 8: Distribution of the number of children by low birth weight and sex|
Click here to view
In our study, severely affected patients presenting with cystic encephalomalacia were only 25.93% (n = 14) whereas majority, i.e., 74.07% (n = 40) lack this finding. Gender difference between the two groups was statistically insignificant [Table 9] and [Graph 9].
|Table 9: Distribution of the number of children by cystic encephalomalacia and sex|
Click here to view
In the present study, dimensions of different parts of CC were in order of isthmus <body <splenium <genu. Thus, thickest part was genu (male - 6.14 mm, female - 5.33 mm) followed by splenium, and thinnest part is isthmus (male - 1.87 mm, female - 1.90 mm). Descending order of thinning was isthmus >body >splenium >genu. Thinning of isthmus was slightly more in male (mean width 1.87 mm) patients than female (mean width 1.90) [Table 10] and [Graph 10].
|Table 10: Comparison of male and females with respect to different variables by t-test|
Click here to view
In our study, most of the CC dimensions did not differ much between male and female patients, but the FOD was slightly larger in females [Graph 11].
In the present study, various dimensions in general seem to be increasing with increasing age of the patient. Minimum dimensions were observed in isthmus part followed by body of CC [Table 11].
In the present study as suggested by P value calculated using Karl Pearson's correlation coefficient method, the correlation between various dimensions and age was statistically significant for APD (P = 0.0065), LCC (P = 0.0022), GT (P = 0.0001), BT (P = 0.0011), ST (P = 0.0369), and FOD (P = 0.0001). For isthmus difference of age groups was insignificant [Table 12].
|Table 12: Correlation between age of children and different variables by Karl Pearson's correlation coefficient method|
Click here to view
| Discussion|| |
HIE remains one of the major causes of mortality and morbidity in neonates. Brain hypoxia and ischemia due to systemic hypoxemia, reduced CBF, or both are the primary physiological processes that lead to HIE.,, Neonatal HIE occurs in one to six per 1000 live full-term births. Of affected newborns, 15%–20% of affected newborns will die in the postnatal period, and an additional 25% will sustain childhood disabilities.,
Acute profound HIE tends to produce selective injury to the parts of the brain with the highest metabolic demands reflected by ongoing myelination. This leads to typical pattern of injury seen on MRI. Accurate identification and characterization of the severity, extent, and location of brain injury rely on the selection of appropriate neuroimaging modalities, including US, CT, and MRI.
Conventionally, US used to be the first-line imaging technique for the evaluation of the newborn brain. In the present times, MRI has become the state of the art imaging modality. Newer diagnostic techniques such as diffusion-weighted MRI and MR spectroscopy provide further insight into HIE and the potential for possible therapeutic intervention.
Studies of patients with agenesis of the CC or commissurotomy have demonstrated that the CC plays an important role in establishing hemispheric lateralization of function. The significance of this structure which is the primary white matter commissure of the brain lies in the fact that damage to the CC during development has been found to be associated with poor neurological outcome and neuropsychological performance.
In quite, a few studies, there has been established the direct quantitative correlation between thickness of the CC and volume of cerebral white matter in children with CP and developmental delay. The data of biometry of CC in HIE patients are scarcely available. Hence, this study is an effort toward drawing a conclusion about the growth pattern of CC in such patients.
A total of 54 patients fulfilled the selection criteria as suggested in the inclusion and exclusion criterion. During the study, that is, from January 2015 to December 2015, the study was carried out in 54 patients having history of birth asphyxia and presenting with neurological disabilities. Morphometric analysis of the corpus callosal dimensions of the patients was made on available mid-sagittal T1-weighted images at the level of cerebral aqueduct in hospital's PACS. All the MRI scans were done using Siemens MAGNETOM Symphony 1.5T using the head coils.
In the present study, males outnumbered females, i.e., 77.78% of the patients were male, and 22.22% were female with male to female ratio as 3.5:1.
We included the patients up to the age of 18 years in the present study. This was for the purpose of evaluating the changes in morphology of CC in long-term in adolescents as antecedents of HIE. The maximum numbers of patients were under 1 year of age while the second largest group of patients belonged to the age group between 1 and 2 years, with a mean age of 3.05 years. This can be attributed to the fact that encephalopathy due to hypoxic-ischemic injury usually manifests within the first few hours after birth. In addition as suggested in the previous studies that despite improvements in perinatal care, asphyxia remains a major cause of mortality, resulting in up to 25% of perinatal mortality and morbidity and giving rise to between 8 and 15% of all cases of CP.
The present study demonstrated that majority were born preterm 77.78% as compared to term infants 22.22%. Moreover, males (76.19%) outnumbered females (23.81%) among preterm patients. To understand predilection of preterm children, we need to consider embryological data. As the literature says, the CC originates at 10–11 weeks gestation and first develops rostrally to form the genu. Other parts of the CC, the rostrum (continuous below with the genu) and the splenium are formed after the trunk is developed, and by 16 weeks, the shape of the adult CC is recognizable. In its early development, the genu grows faster than the splenium which does not show a rapid growth until after birth. Thus, the later development of the splenium and posterior area of the CC make them particularly susceptible to damage in the third trimester and perinatal period.
Another fact, we observed that most of the patients were having a history of NICU stay after birth as many as 77.78% of total patients. This indirectly correlated with severity of hypoxic injury and in turn the severity of damage to CC.
Apgar score is another important variable for making the clinical diagnosis of birth asphyxia. As observed in our study, all patients were having score of <3. Moreover, maximum patients fell in the category of score 2 with 55.56% patients in this group followed by 29.63% patients with Apgar score of 3. This finding is in accordance of the fact that for diagnosis of HIE the Apgar score should be ≤3.
In our study, maximum patients (75.93%) were having a history of no cry at birth compared to 24.07% who cried at birth. This factor is also in consistency with the literature which establishes this as an evidence of hypoxic injury and its consequences.
The CC is a cerebral structure that reflects cognitive status in several neurological pathologies. Visual inspection of MRI has shown that HIE causes callosal damage. Periventricular leukomalacia caused by hypoxia-ischemia damage the periventricular crossroads of commissural, projection, and associative pathways, which are in a close topographical relationship with the lateral ventricles. MRI has facilitated diagnostic assessment of the CC. We tried in our study to explore to what extent HIE leads to changes in size of the CC.
Distances measured between different landmarks identified on the CC have also been evaluated. We observed that true LCC (mean length ≈ 60 mm) was larger than APD of CC (mean length ≈ 50 mm). GT was the thickest part followed by ST whereas IT was the thinnest followed by body of CC (BT). FODs were slightly higher in males (mean 128.59 mm) than females (mean 120.25 mm). The ratio of IT/ST was more in females as compared to males (females - 0.78, males - 0.56) as well as ratio of APD/FOD. Our results are in keeping with studies evaluating CC growth in older children and confirm progressive increase in CC length throughout childhood. While considering subregions of the CC, in the previous studies some authors showed differences in the size of CC subregions likewise ours'. However, unlike these authors, we could not observe a predominant increase in CC posterior subregions (ST in our study) during childhood and adolescence as we included only HIE-affected patients. No controls were included in our study.
We observed that true LCC was minimum in <1 year age group and maximum in 9–16 years age group. Dimensions of isthmus part did not vary greatly in various age groups as it has limited range extending from mean value of 1.64–2.28 mm. Thus, it favors our hypothesis that there is focal reduction in CC fibers with a certain pattern affecting posterior part more than anterior because of the growth pattern explained in literature and positively correlating with most vulnerable part getting damaged during perinatal periods of stress.
| Conclusion|| |
To conclude our study data demonstrate that besides various established HIE manifestations corpus callosum is yet another important structure to be studied. Our study is one of the few studies providing biometric data of the CC in HIE affected children from birth to 18 years. Our findings shows that preterm birth in addition adversely affects the development of CC as most of the patients were born preterm. Most common site of injury was posterior part including isthmus and body where thinning secondary to loss of commissural fibers was found. There was no sex effect observed in the size or morphology of the CC.
Magnetic resonance imaging is valuable non-invasive, radiation free tool with multiplanar capabilities which not only provides precise information regarding morphometry of corpus callosum but is also helpful in identifying the exact extent and site of the injury and other associated findings thus helping in the further management of the patient.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ferriero DM. Neonatal brain injury. N
Engl J Med 2004;351:1985-95.
Perlman JM. Brain injury in the term infant. Semin Perinatol 2004;28:415-24.
Grow J, Barks JD. Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: Current concepts. Clin Perinatol 2002;29:585-602, v.
Gunn AJ. Cerebral hypothermia for prevention of brain injury following perinatal asphyxia. Curr Opin Pediatr 2000;12:111-5.
Vannucci RC, Perlman JM. Interventions for perinatal hypoxic-ischemic encephalopathy. Pediatrics 1997;100:1004-14.
Robertson CM, Finer NN, Grace MG. School performance of survivors of neonatal encephalopathy associated with birth asphyxia at term. J Pediatr 1989;114:753-60.
Shankaran S, Woldt E, Koepke T, Bedard MP, Nandyal R. Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants. Early Hum Dev 1991;25:135-48.
Barkovich AJ, Sargent SK. Profound asphyxia in the premature infant: Imaging findings. AJNR Am J Neuroradiol 1995;16:1837-46.
Felderhoff-Mueser U, Rutherford MA, Squier WV, Cox P, Maalouf EF, Counsell SJ, et al.
Relationship between MR imaging and histopathologic findings of the brain in extremely sick preterm infants. AJNR Am J Neuroradiol 1999;20:1349-57.
Hüppi PS. Advances in postnatal neuroimaging: Relevance to pathogenesis and treatment of brain injury. Clin Perinatol 2002;29:827-56.
Back SA, Gan X, Li Y, Rosenberg PA, Volpe JJ. Maturation-dependent vulnerability of oligodendrocytes to oxidative stress-induced death caused by glutathione depletion. J Neurosci 1998;18:6241-53.
de Guise E, del Pesce M, Foschi N, Quattrini A, Papo I, Lassonde M. Callosal and cortical contribution to procedural learning. Brain 1999;122(Pt 6):1049-62.
Garel C, Cont I, Alberti C, Josserand E, Moutard ML, Ducou le Pointe H. Biometry of the corpus callosum in children: MR imaging reference data. AJNR Am J Neuroradiol 2011;32:1436-43.
Ramaekers G, Njiokiktjien C. Embriology and anatomy of the corpus callosum. The Child's Corpus Callosum. Amsterdam: Suyi; 1991. p. 25-39.
Cumming WJ. An anatomical review of the corpus callosum. Cortex 1970;6:1-18.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12]