Germinal Matrix Hemorrhage Imaging

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Germinal matrix hemorrhage (GMH) and intraventricular hemorrhage (IVH) are the most common and most important neurologic injuries in preterm neonates. The brain of a premature infant lacks the ability to autoregulate cerebral blood pressure; thus, fluctuations in cerebral blood pressure and flow can rupture the primitive germinal matrix vessels or lead to infarction of the metabolically active germinal matrix. The damage can extend into the periventricular white matter, resulting in significant neurologic sequelae, including cerebral palsy, mental retardation, and seizures. Injury to the germinal matrix has substantial mortality and morbidity rates.

A common lesion that characterizes the neuropathology of GMH/IVH is bleeding into the subependymal germinal matrix, with or without subsequent rupture into the lateral ventricle (see the images below). Sequelae of GMH/IVH include germinal matrix destruction, periventricular hemorrhagic infarction with subsequent encephalomalacia, and posthemorrhagic hydrocephalus. ^{[1, 2, 3, 4]}

Ultrasonography is the primary imaging modality for the screening and diagnosis of GMH/IVH, and computed tomography (CT) scanning and magnetic resonance imaging (MRI) are used as supplementary tools (see the images above).

The IVH grading system created by Burstein et al in 1979 relies on the detection of blood in the subependymal germinal matrix and the ventricles, as follows ^[5] :

Grade 1: Hemorrhage that is confined to the germinal matrix

Grade 2: Extension of the hemorrhage into the lateral ventricles without hydrocephalus

Grade 3: Ventricular hemorrhage with the presence of associated hydrocephalus

Grade 4: Parenchymal hemorrhage

Ultrasonography is the preferred screening and diagnostic tool for GMH. ^{[6, 7]} The portability of this modality allows imaging in the nursery with minimal disturbance of the infant. Ultrasonography also depicts GMHs that are larger than 5 mm, with a sensitivity of nearly 100% and specificity of 91%. Smaller GMHs, however, are more difficult to identify. Power and pulsed-wave Doppler ultrasonography can be used to identify preterm neonates who are at risk for GMH and IVH during their first week of life. Using this modality, clinicians can detect autoregulatory fluctuations in the preterm neonate’s cerebral blood flow with examination of the lenticulostriate arteries; measurements of the peak velocity, resistive index, and coronal vascular cross-sectional area; and product of the peak velocity and vascular cross-sectional area. ^{[8, 9, 10]}

CT scanning and MRI are also used and have better interobserver agreement. ^[11] Because these modalities more readily depict small GMHs, CT scanning and MRI have a higher sensitivity than that of ultrasonography. However, these 2 imaging modalities require that the infant be moved from the nursery; there is also the possibility that sedation would be required. ^{[12, 13]}

All imaging modalities have relatively low negative predictive values (NPVs). In a 2000 study, Blankenberg et al found negative predictive values of 53% at 2-month follow-up and 59% at 2-year follow-up, irrespective of the modality. ^[14] However, the absence of neuroimaging abnormalities in the infant does not exclude the possibility of later neurodevelopmental problems.

Periventricular leukomalacia is included in the differential diagnosis.

Normal imaging findings must be viewed with caution. Ultrasonography, CT scanning, and MRI all have low negative predictive values of approximately 60%.

With fetal ultrasonography and fetal MRI, GMH/IVH can be identified in utero, remote in time from delivery. ^[15]

Intraventricular hemorrhage (IVH) evolves in a predictable pattern. Acutely, it appears to hyperattenuate. After 7-10 days, the hemorrhage becomes isoattenuating relative to the brain parenchyma. Later, with clot retraction, a subependymal hematoma may develop into a fluid-filled cyst. The affected brain parenchyma may undergo atrophy and gliosis (see the following image below).

Blankenberg et al found that CT scanning had nearly twice the sensitivity of ultrasonography in the detection of germinal matrix hemorrhage (GMH) and IVH; interobserver agreement with this modality was also improved relative to ultrasonography. ^[14]

A normal CT scan finding for GMH and IVH does not exclude abnormal neurodevelopment; the negative predictive value is 50-60% at age 2 years.

In the first 3 days after intraventricular hemorrhage (IVH), subependymal hematomas are isointense to slightly hypointense on T1-weighted MRIs (T1WIs) and markedly hypointense on T2-weighted MRIs (T2WIs). In the early subacute stage during days 4-7, the signal intensity increases on T1WIs. In the late subacute stage during days 7-14, the signal intensity increases on T2WIs. Over the next several months, the hemorrhage becomes hypointense on images obtained with both sequences, and ferromagnetic effects secondary to hemosiderin and ferritin predominate (see the images below in Multimedia). ^[12]

As with CT scanning, Blankenberg et al found that MRI had nearly twice the sensitivity of ultrasonography in the detection of germinal matrix hemorrhage (GMH) and intraventricular hemorrhage (IVH), and interobserver agreement with this modality was also improved relative to ultrasonography. ^[14]  A normal image finding for GMH/IVH does not exclude abnormal neurodevelopment. The negative predictive value is 50-60% at age 2 years.

Neurosonography is the primary modality for both screening and follow-up of germinal matrix hemorrhage (GMH) and intraventricular hemorrhage (IVH) in neonates. Ultrasonography is portable, allowing imaging in the comfortable environment of the neonatal intensive care unit (NICU), this modality has negative predictive values similar to those of CT scanning and MRI. Current screening protocols recommend performing ultrasonographic studies on days 7-14 of life and between the fourth and sixth weeks of life. Many centers offer more frequent screening. ^{[16, 8, 9]}

On ultrasonograms, acute subependymal hemorrhage appears as a homogeneous echogenic mass, often in the caudothalamic groove (see the image below).

The hematoma becomes less echogenic over time, beginning with the central portion. Subsequent to eventual clot retraction, a subependymal cyst may develop, or a linear echo may result (see the following image).

Acutely, IVH also appears echogenic. Cerebrospinal fluid (CSF)–blood fluid levels may be observed. When large, the clot forms a cast of the ventricle (see the image below) and may break up in the ventricle, resulting in low-level echoes that float in the CSF.

The clot may also move when the patient’s head position changes. With clot evolution, the hematoma becomes echolucent, starting centrally (see the following images). Scanning through the posterior fontanelle may optimize visualization of occipital horn clots.

Intraparenchymal hemorrhage is usually located in the frontal and parietal lobes and appears acutely as an echogenic homogeneous mass. As the hemorrhage evolves, an echogenic rim with a sonolucent center forms. After 2-3 months, a porencephalic cyst (if the lesion communicates with a ventricle) or encephalomalacia may develop (see the image below).

Power and pulsed-wave Doppler ultrasonography may be useful in identifying preterm neonates who are at risk of GMH/IVH during their first week of life. The ultrasonograms may depict autoregulatory fluctuations in cerebral blood flow. Neurosonography depicts GMHs that are larger than 5 mm with a sensitivity of 100% and a specificity of 91%. IVH may blend imperceptibly with the choroid plexus, which has a similar echo texture; thus, asymmetric thickness of the choroid plexus should be viewed with suspicion. The lack of abnormality with ultrasonography does not exclude the possibility of later neurodevelopmental problems.

Simard JM, Castellani RJ, Ivanova S, Koltz MT, Gerzanich V. Sulfonylurea receptor 1 in the germinal matrix of premature infants. Pediatr Res. 2008 Dec. 64(6):648-52. [Medline].

Roze E, Kerstjens JM, Maathuis CG, ter Horst HJ, Bos AF. Risk factors for adverse outcome in preterm infants with periventricular hemorrhagic infarction. Pediatrics. 2008 Jul. 122(1):e46-52. [Medline].

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Omar Islam, MD, FRCPC Assistant Professor of Radiology, Queen’s University Faculty of Health Sciences; Consulting Staff, Department of Imaging Services, Section Head, Division of Neuroradiology and Head and Neck Imaging, Kingston General Hospital and Hotel Dieu Hospital, Canada

Omar Islam, MD, FRCPC is a member of the following medical societies: Canadian Medical Association, Ontario Medical Association, American Society of Neuroradiology, Radiological Society of North America

Disclosure: Nothing to disclose.

Andrew Leung, MD 

Andrew Leung, MD is a member of the following medical societies: College of Physicians and Surgeons of Ontario

Disclosure: Nothing to disclose.

Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand

Disclosure: Nothing to disclose.

Kieran McHugh, MB, BCh Honorary Lecturer, The Institute of Child Health; Consultant Pediatric Radiologist, Department of Radiology, Great Ormond Street Hospital for Children, London, UK

Kieran McHugh, MB, BCh is a member of the following medical societies: American Roentgen Ray Society, Royal College of Radiologists

Disclosure: Nothing to disclose.

Eugene C Lin, MD Attending Radiologist, Teaching Coordinator for Cardiac Imaging, Radiology Residency Program, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine

Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, Society of Nuclear Medicine and Molecular Imaging

Disclosure: Nothing to disclose.

Charles M Glasier, MD Professor, Departments of Radiology and Pediatrics, University of Arkansas for Medical Sciences; Chief, Magnetic Resonance Imaging, Vice-Chief, Pediatric Radiology, Arkansas Children’s Hospital

Charles M Glasier, MD is a member of the following medical societies: American College of Radiology, American Society of Neuroradiology, Radiological Society of North America, Society for Pediatric Radiology

Disclosure: Nothing to disclose.

Germinal Matrix Hemorrhage Imaging

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