Comparison of Findings on Cranial Ultrasound and Magnetic Resonance Imaging in Preterm Infants

DISCUSSION

Cranial US remains the main clinical tool for imaging the preterm infant brain. However, there is considerable controversy particularly about the significance of WM echogenicities in the preterm infant. Comparison of US with MRI findings may enable better understanding of their cause and prediction of clinical outcome, although the clinical significance of signal intensities, particularly DEHSI in WM on MRI in preterm infants, remains to be established.

In this study, we compared findings on reproducible hard-copy cranial US scans with findings on MRI performed on the same day. This method of obtaining and recording US images is identical to the day-to-day clinical practice in many neonatal intensive care units, although, unlike our study, information from preceding scans is usually available. The quality of hard-copies images depends on the type of printing paper used and the brightness/contrast settings of the printer. Hence, many clinicians might prefer to analyze cranial US scans on line but in practice most use hard copy. In addition, clinical records require the acquisition of reproducible copies of US scans.

We calculated the value of findings on a single US scan as a predictor of MRI signal intensity. Each US scan was analyzed, clinically and statistically, as a separate entity without reference to serial findings on previous or subsequent images.

US provides less even coverage of the brain compared with MRI making identification of abnormalities in deeper and peripheral structures such as the basal ganglia, posterior fossa, and cortex more difficult. However, cranial US is thought to be reliable at detecting lesions such as IVH, GLH, and HPI. Reported sensitivity of US in predicting the presence of IVH, GLH, and HPI at necropsy varies from 50%²³ in some studies to 91% in others.²⁴The specificity in these studies varied from 100%²³ to 85%.²⁴

There is less agreement about the clinical and pathologic significance of WM echogenicities on cranial US scans. Both the degree^25,26 and the duration^3,27–29 of WM periventricular echogenicities have been related to WM necrosis at necropsy and to neurodevelopmental disability. However, nonhemorrhagic WM necrosis may show no abnormality on cranial US scans.²⁵The reported sensitivity of cranial US predicting the presence of WM lesions at necropsy ranges from 85%²⁴ to 67%¹⁰ and 28%.² The specificity in these studies varied from 93%²⁴ to 86%.² In one additional study, the specificity of US in predicting WM lesions at necropsy varied from 50% to 92% with different US interpreters.³⁰

MRI has been used to obtain brain images during follow-up of ex-preterm infants and children^31–34 but the systematic use of magnetic resonance imaging (MRI) in sick extremely low birth weight infants has been impractical. It is now possible to perform serial imaging safely to study brain development and to provide information on the timing and evolution of brain injury.³⁵

There are very few studies that compare brain MRI findings with histopathologic findings in preterm infants¹⁸ and fetuses.^16,17 However, MR is an accurate technique for diagnosing hemorrhagic brain lesions. GLH, IVH, HPI, and small petechial WM hemorrhages in preterm infants can be accurately detected using MRI.¹³ In addition, it has been suggested that MRI is superior to autopsy in diagnosing IVH.¹⁷ This is because the lengthy formalin preservation required for preterm brains may result in leakage of intraventricular blood from a hemorrhage,¹⁷ making the diagnosis of IVH more difficult at autopsy if the examination is delayed.

Detailed WM structure, including layers of migrating glial cells, are also clearly illustrated using brain MRI.^13–16 In a recent study comparing brain MRI to histopathologic findings in preterm infants, excessively low signal intensity on FSE inversion recovery images in the periventricular WM corresponded to areas of necrosis.¹⁸ In addition, in a recent cohort of preterm infants, diffuse/excessive high signal intensity on FSE T2-weighted images and low-signal intensity on FSE inversion recovery images was closely associated with the development of features suggestive of cerebral damage, such as dilatation of the lateral ventricles, widening of the extracerebral space, and the interhemispheric fissure at term.²¹ Changes in signal intensity on MRI may therefore correspond to nonhemorrhagic WM lesions.

The results of this study showed that US was a good predictor for the presence of GLH, IVH, and HPI on MRI. Slightly more GLH was thought to be present on US on the early scans than was seen on MRI, indicating that it is easy to overestimate this diagnosis just after birth. The appearances may occur for the same reason as that of choroid plexus echogenicity, the cause of which is not known, which was often seen on early scans but not found to be hemorrhagic on MRI (see below). In the Group B scans, more GLH was seen on MRI. This may be because resolving GLH may seem normal on US, but irregularity and persisting low-signal intensity of the germinal matrix remains easily detectable on MRI. The late appearances of GLH on US not confirmed on MRI may be attributable to nonhemorrhagic echogenicity seen in this region that has been reported in older preterm infants.³⁶

Not all IVH's were detected by US. MRI detected small IVH's in the depth of the posterior horns, which were not seen on US, probably because their site was relatively inaccessible to transfontenellar US. If the infants had been examined with US through the posterior fontanelle they might have been detected. It is unlikely that they were of any clinical significance.

Choroid plexus echogenicity was commonly seen on initial and repeat US scans, but was much less common at term. The cause and clinical relevance of choroid plexus echogenicity is not known. The choroid plexus is difficult to see on MRI unless there is hemorrhage within it or intravenous contrast is given. These choroid plexus echogenicities seen on US are, therefore, probably not related to hemorrhage, but may be related to relatively high blood flow in first days after birth. Similar appearances are also seen in term infants and they do not seem to carry any clinical significance.³⁷ Posterior fossa echogenicity within the cerebellum was seen in an equal number of infants on early and term US scans but no posterior fossa abnormalities were seen; in particular, no evidence of hemorrhage was documented on MRI. The cause and clinical relevance of cerebellar echogenicity on US is not known.

Severe echogenicities within the basal ganglia were associated with basal ganglia hemorrhage on MRI, but small petechial hemorrhages in the head of the caudate nucleus that were present on MRI in 3 infants were not associated with echogenicity on US. This is not likely to be of any clinical significance, although some persisting biochemical abnormality has been detected in the caudate nuclei following GLH.³⁸

There were only a few infants with echolucencies on US and none with frank cystic periventricular leukomalacia. This made it difficult to compare the accuracy of US in predicting the presence of cysts on MRI.

For the purpose of this study, WM echogenicity on US was assessed as a predictor of WM hemorrhage and/or DEHSI on T2-weighted images on MRI. On the early scans, WM echogenicity was common but not usually associated with the presence of hemorrhage or DEHSI on T2-weighted images on MRI. Even when echogenicity was severe, MRI scans could look normal This finding is consistent with what is already known (ie, that WM echogenicities in the first week after birth may be transient and of benign significance).²⁸

WM echogenicities on US scans performed at a postnatal age >7 days co-occurred with MRI abnormality more often. All infants with severe echogenicity and 4 of 6 with moderate echogenicity had abnormal MRI scans, and half of the infants with mild echogenicity had abnormal MRI scans. All US scans in this interim period were thought abnormal when the MRI scan was abnormal. However, mild abnormality on US could be associated with a normal MRI scan.

In the later Group C scans, US was abnormal in most but not all infants where DEHSI was seen on MRI.

Thus severe WM echogenicity beyond the first week generally correlated with abnormality on MRI when the co-occurrence of US echogenicity and DEHSI occurred in ∼2/3 of the infants. This suggests that they may often represent the same process. Significantly, normal WM on US did not always predict normal WM on MRI. The physics of the 2 techniques is completely different, and normal developmental and pathologic processes may not be reflected with equal conspicuity. It is known that hemorrhage may remain visible on MRI for weeks, and longer than it is seen on US. The time course of nonhemorrhagic WM changes may also be different on US than on MRI.

A recent study¹⁹ compared WM findings on single MRI's performed at a mean GA of 33.4 (range: 30.6–37) weeks (mean age at MRI: 18.7 days) with findings on serial US scans including 1 performed on the same day as MRI. The infants all had normal neurologic examinations, and the WM on US was either normal or had mild echogenicities. A zone of high-signal intensity on T2-weighted images in the periventricular WM was reported to be associated with periventricular WM echogenicities on US. The authors concluded that MRI is probably more sensitive than US in early detection of mild periventricular WM lesions in preterm infants.¹⁹ No later MRI scans were performed, and therefore the evolution of the echogenicities could not be compared with the evolution of signal intensity on MRI. Our finding of DEHSI in the WM is probably similar to the high-signal intensity on T2-weighted images described in that study. The clinical significance of DEHSI is not yet known. It may partly reflect abnormal maturation rather than a pathologic process, and ongoing studies will correlate it with indices of perinatal sickness and infection, follow-up MRI scans, head growth, and neurodevelopmental outcome.