Quantitative morphologic evaluation of magnetic resonance imaging during and after treatment of childhood leukemia

Abstract

Introduction: Medical advances over the last several decades, including CNS prophylaxis, have greatly increased survival in children with leukemia. As survival rates have increased, clinicians and scientists have been afforded the opportunity to further develop treatments to improve the quality of life of survivors by minimizing the long-term adverse effects. When evaluating the effect of antileukemia therapy on the developing brain, magnetic resonance (MR) imaging has been the preferred modality because it quantifies morphologic changes objectively and noninvasively.

Method and results: Computer-aided detection of changes on neuroimages enables us to objectively differentiate leukoencephalopathy from normal maturation of the developing brain. Quantitative tissue segmentation algorithms and relaxometry measures have been used to determine the prevalence, extent, and intensity of white matter changes that occur during therapy. More recently, diffusion tensor imaging has been used to quantify microstructural changes in the integrity of the white matter fiber tracts. MR perfusion imaging can be used to noninvasively monitor vascular changes during therapy. Changes in quantitative MR measures have been associated, to some degree, with changes in neurocognitive function during and after treatment.

Conclusion: In this review, we present recent advances in quantitative evaluation of MR imaging and discuss how these methods hold the promise to further elucidate the pathophysiologic effects of treatment for childhood leukemia.

Fig. 1

Transverse images from a patient after completion of consolidation therapy for ALL are shown. Images from left to right are T1-weighted, T2-weighted, PD-weighted, and FLAIR. T2 hyperintensities are clearly evident throughout the periventricular and deep white matter

Fig. 2

A single transverse section from a FLAIR imaging set is shown on the left. The middle image is a quantitative T2 relaxation map of the same section. The corresponding quantitative T1 relaxation map is shown on the right. T2 relaxation rates in the T2 hyperintense regions are 20-60% longer than the surrounding normal-appearing white matter. The regions of greatest T2 relaxation change demonstrate T1 relaxation rates which are 25% longer than the surrounding normal-appearing white matter. Other regions of T2 hyperintensity which are clearly visible on the T2 relaxation map are indistinguishable from normal-appearing white matter on the T1 relaxation map

Fig. 3

T2-weighted and FLAIR images from a patient after completion of consolidation therapy for ALL are shown on the left and middle, respectively. The corresponding tissue volume map is shown on the right with the T2 hyperintense regions segmented orange to contrast with the normal-appearing white matter shown in green

Fig. 4

Coregistered combination of conventional imaging, tissue volume maps, and quantitative relaxation maps of the same section. The T2 hyperintense regions are visualized on the conventional FLAIR image (a) while those regions are shown in orange on the segmented tissue volume map (b). The relaxation maps of T2 (c) and T1 (d) demonstrate the relative increase in relaxation times for these same regions

Fig. 5

Sagittal, coronal, and transverse images of patients aged less than 5 years (left) who demonstrated LE on second examination (P<0.001), and patients aged 5 years and more (right) who demonstrated LE on second examination (P<0.05). The color bar indicates F-values from statistical analysis with a cluster threshold of 100. Overlay is on the average T2 custom template

Fig. 6

A segmented tissue map from a normal-appearing examination from a patient with sickle cell disease is shown on the left. The image on the right is a quantitative arterial spin labeling map of cerebral blood flow at this same level. This technique assesses blood flow without the use of contrast medium and could potentially be advantageous for evaluation of patients treated for ALL

Fig. 7

A transverse FLAIR image is shown with T2 hyperintensities (a). The fractional anisotropy or FA map (b) demonstrates decreased anisotropy in the hyperintense regions. The genu and splenium of the corpus callosum and the internal capsule show high levels of anisotropy as would be expected for these regions of highly directional fiber tracts. The apparent diffusion coefficient or ADC map (c), perpendicular diffusion or D_⊥ map (d), and the parallel diffusion or D_∥ map (e) all demonstrate increased diffusion in the regions of hyperintensity

Fig. 8

T2-weighted (top row) and diffusion-weighted (bottom row when available) images from a longitudinal imaging examination in a patient who presented with right-sided weakness 7 days post IT-MTX. The T2-weighted image is normal (a) and the patient was scheduled for a repeat examination including diffusion-weighted imaging 4 days later. Areas of well-defined focal T2 hyperintensities are seen in the centrum semiovale (b) with corresponding areas of restricted diffusion (e). Symptoms resolved in 2 weeks with no intervention, and imaging was repeated. The previous areas of T2 hyperintensities are now larger and more diffuse (c), and the area of restricted diffusion now demonstrates slightly increased diffusion (f). Imaging obtained 7 months later show a marked decrease in the extent and intensity of the T2 hyperintensities (d)