Tumor volume or dynamic contrast-enhanced MRI for prediction of clinical outcome of Ewing sarcoma family of tumors.

BACKGROUND: The identification of risk factors that predict poor clinical outcome at the time of diagnosis could lead to intensified early therapy and improved outcome for pediatric patients with Ewing sarcoma family of tumors (ESFT). OBJECTIVE: To compare the effectiveness of static magnetic resonance (MR) imaging measurements of tumor volume with variables obtained by dynamic contrast-enhanced MR imaging (DEMRI) in predicting ESFT outcome. METHODS: MR examinations that included DEMRI were retrospectively reviewed. The analyses included 45 examinations of 21 patients with ESFT (performed from 1992 to 1996). Tumor volumes were measured on the static MR images, and the regions of interest were selected for DEMRI analysis. The relationships of static MR imaging and DEMRI variables with the probability of progression-free survival (PFS) and disease-free survival (DFS) were determined. RESULTS: Larger tumor volume at the time of diagnosis predicted poorer PFS and DFS estimates. No DEMRI variable predicted outcome. CONCLUSION: Determination of tumor volume by static MR imaging at the time of diagnosis is a simple and reliable method of predicting the clinical outcome of patients with ESFT. DEMRI is not as reliable a technique as static MR imaging for predicting the outcome of these patients.

Fast adipose tissue (FAT) assessment by MRI.

We report a method of fast adipose tissue (FAT) assessment to characterize the quantity, and distribution of abdominal adipose tissue. Whole-volume coverage of the abdomen was obtained using 31 contiguous transverse T(1)-weighted images from 16 obese females. A radiologist manually traced all adipose tissue volumes in the images, while a physiologist used an automated method to measure adipose tissue in a single image at the level of the umbilicus. Automated analysis of the umbilicus-level image was significantly correlated with values obtained by manual analysis of the entire abdomen (p < 0. 001). There was good agreement between the automated umbilicus-level image method and the manual whole abdomen method for subcutaneous adipose tissue (r(2) = 0.958), visceral adipose tissue (r(2) = 0. 753), and total adipose tissue (r(2) = 0.941). The automated method required 6 min vs 2 h for the manual method.

Accuracy of MR imaging for detecting epiphyseal extension of osteosarcoma.

BACKGROUND: Too few patients are receiving epiphyseal-sparing limb salvage procedures for osteosarcoma. OBJECTIVE: To determine how magnetic resonance (MR) imaging can best predict the epiphyseal extension of osteosarcoma. MATERIALS AND METHODS: Forty children underwent complete pretreatment static and dynamic contrast-enhanced MR imaging (DEMRI). Static MR images [T1-weighted and short tau inversion recovery (STIR)] of the epiphyses were read in three ways: (1) for suspicion of any abnormality (tumor or edema), (2) for suspicion of tumor, excluding suspected edema, and (3) validating the second method by using a scale to rate the likelihood of tumor. Presentation imaging was compared to histopathologic findings after chemotherapy and resection. The receiver operating characteristic (ROC) method was used to analyze the scaled ratings of static MR and DEMRI values. RESULTS: At delayed resection, 20 of 40 children with osteosarcoma had confirmed epiphyseal tumor; however, 32 epiphyses were abnormal on STIR and 28 abnormal on T1. Differentiating suspected tumor from edema increased the accuracy to an Az (area under the ROC curve) of 0.94 for both T1-weighted and STIR static sequences. T1-weighted MR had better specificity and STIR better sensitivity at any given rating. DEMRI was slightly less accurate (Az = 0.90). CONCLUSION: Static MR imaging most accurately detected epiphyseal extension of osteosarcoma when readers distinguished suspected tumor from edematous or normal tissue.

Improved MR imaging for patients with metallic implants.

Pediatric oncology patients with large metallic prostheses were imaged with one of two MR imaging techniques: 1) the "tilted view-angle" technique, 2) or a higher readout bandwidth technique. The tilted view-angle method uses an additional gradient in the slice selection direction during readout. The high bandwidth technique increases the readout bandwidth and shortens the echo time (TE). High bandwidth and short echo times were implemented in both T(1)-weighted (T(1)W) turbo spin echo and turbo short tau inversion recovery (STIR) sequences. Both imaging techniques reduced the size of metal-induced image artifacts. The tilted view-angle method reduced the artifact to a greater degree but had inherent shortcomings. The reformatted images were blurred and shifted. The area of interest was often moved outside of the field of view, unless parameters were adjusted on the basis of a pre-scan calculation. The high readout bandwidth, short echo technique required no special preparation and reduced metal artifacts without image blurring. The combination of high-bandwidth, shorter echo turbo STIR and T(1)W turbo spin echo sequences with subtraction of pre- from post-contrast images allowed effective fat suppression without local field inhomogeneity affects. This greatly improved our ability to evaluate suspected disease near metallic implants in pediatric cancer patients.

3D gadolinium-enhanced MRA: evaluation of hepatic vasculature in children with hepatoblastoma.

We used contrast-enhanced three-dimensional magnetic resonance angiography (3D MRA) modified for pediatric use to evaluate the hepatic vasculature prior to partial hepatectomy in five consecutive children with hepatoblastoma. Modifications included non-breath-hold technique in four of the five children who were sedated. The single breath-hold technique was performed in only one awake child. Scan delay times were based on contrast infusion time rather than total infusion time. The hepatic artery, portal vein, and inferior vena cava were identified in all patients. MRA findings were confirmed by conventional angiography in one patient and by surgery in all. Contrast-enhanced 3D MRA is a useful and rapid technique prior to partial hepatectomy in patients with hepatoblastoma.

Effective use of the web to expand a summer predoctoral program: the St. Jude experience.

BACKGROUND: Since 1978, the St. Jude Children's Research Hospital has oncology education (POE) program for medical and other health professional students to do two-to-four-month clinical and/or basic research rotations in pediatric oncology. Limitations in funding, recruitment capability, and faculty interest held student numbers to 0-18 per year. METHODS: In early 1997, the program announcement and an on-line application were put on the Web site, . An applicant's online submission is delivered immediately to the program director's e-mail inbox, promptly acknowledged via e-mail, transferred to a digital database, and forwarded electronically to prospective institutional preceptors. RESULTS: The program accepted 36 of 61 applicants (56% minority) in 1997. A supplemental funding award enabled expansion of the program to include students preparing for health professions or biomedical sciences careers. In 1999, 75 of 139 applicants were accepted (47% minority) from 39 schools in 18 states, the District of Columbia, Puerto Rico, Mexico, and Ireland. CONCLUSIONS: Effective use of the Web and e-mail made it possible to inform students effectively about the institution and program, match students with preceptors, increase the number of minority participants, and expand the regional program into a national one.

Applications of 3D contrast-enhanced MR angiograpy in pediatric oncology.

Contrast-enhanced 3D MR angiography can be used for imaging of children. This technique can improve the delineation of the vasculature that is more anatomically familiar to surgeons. Here we illustrate the usefulness of contrast-enhanced 3D MR angiography in the diagnosis and follow-up of pediatric oncology patients.

Pilot study of noninvasive detection of venous occlusions from central venous access devices in children treated for acute lymphoblastic leukemia.

BACKGROUND: Survivors of childhood acute lymphocytic leukemia (ALL) are at risk of venous occlusion induced by central venous access devices (CVADs). A sensitive, noninvasive screening technique to identify the magnitude of this problem is needed. Ultrasound (US) cannot always adequately image the innominate veins or the superior vena cava. Magnetic resonance angiography (MRA) can be noninvasive and may be useful for screening these patients. OBJECTIVE: We examined the suitability of US and MRA to identify venous occlusion. MATERIALS AND METHODS: We used MRA and ultrasound to examine 11 pediatric patients previously treated for ALL. CVADs had been in place a median of 2.5 years (range, 0.4-2.8 years) and removed a median of 2.1 years (range, 0.6-2.9 years) previously. We also performed 2D time-of-flight magnetic resonance angiography (TOF MRA) on two healthy young adult women with no history of venous abnormality or CVAD use. RESULTS: MRA suggested central venous abnormalities in 8 of the 11 ALL survivors and in both healthy control subjects. US results were negative in all 11 survivors. CONCLUSION: Further investigation is warranted to develop a sensitive and specific noninvasive method for identifying venous occlusion caused by prior CVAD use. Such a method would allow prospective studies of this complication in pediatric ALL survivors.

Curved reconstruction along the anterior optic pathway.

Curved reconstruction of a three-dimensional data set along the anterior optic pathway improves visibility of the optic nerves and chiasm and facilitates comparison between the two nerves. Curved reconstruction reveals three patterns in patients with masses of the anterior optic pathway. Retrobulbar buckling of the optic nerve into a "periscope" configuration is observed in some patients.

Hepatic arterial resistance index--an indicator of diffuse liver disease in children treated with bone marrow transplantation.

AIM: To describe the relationship between the resistance index of the common hepatic artery and liver function tests in children undergoing bone marrow transplantation. MATERIALS AND METHODS: We analysed prospectively the results of 106 Doppler ultrasound examinations of the common hepatic artery from 31 bone marrow transplant patients, 16 of whom had normal liver function. The aetiology of the liver dysfunction in the other 15 patients was veno-occlusive disease (n = 7), unknown (n = 3), hepatic graft-versus-host disease (n = 2), hepatitis (n = 2), or cholestasis (n = 1). We assessed the relationships between the hepatic arterial resistance index (HART) and the results of the serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (ALK), lactate dehydrogenase (LDH) and serum albumin (ALB) assays and calculated HARI break-point values that might distinguish patients with liver disease from patients with the normal liver function. RESULTS: The significant break point (P < 0.05) of the HARI was 0.55 for SGOT, SGPT and ALK. LDH was associated with a break point of 0.53. Resistance indices for the common hepatic artery below the break-point values predicted liver dysfunction with specificities of 81%, 80%, 92% and 93%, respectively. There was no significant relationship between liver function tests and ALB levels. CONCLUSION: If below 0.55, the hepatic arterial resistance index is a non-invasive indicator of liver dysfunction in children undergoing bone marrow transplantation.

Fat-saturated contrast-enhanced T1-weighted MRI in evaluation of osteosarcoma and Ewing sarcoma.

To assess contrast-enhanced (C+), fat-saturated (FatSat), T1-weighted (T1W) imaging in the characterization of the soft tissue mass associated with primary bone tumors, we compared it with T2-weighted (T2W) imaging in patients with osteosarcoma (n = 36) and Ewing sarcoma family of tumors (Ewing sarcoma; n = 11). Periosseous tumor compared with normal muscle had greater contrast-to-noise ratio (CNR) on the FatSat T1W C+ image than on T2W for 81% (38/47; P < .0001) of patients. The CNR of periosseous tumor compared with subcutaneous fat was greater on FatSat T1W C+ for 98% (46/47; P < .0001). Radiologists found it easier to evaluate neurovascular bundle proximity to tumor with FatSat T1W C+ images than with T2W for 64% of patients (30/47; P < .0001). They judged FatSat T1W C+ superior to T2W for periosseous tumor conspicuity and visualization of soft tissue necrosis in 62% (29/47; P < .0001). In patients with osteosarcoma or Ewing sarcoma, FatSat T1W C+ imaging may replace T2W imaging for soft tissue mass evaluation, especially if contrast is being used for dynamic enhancement.

Magnetic resonance imaging for evaluation of childhood aplastic anemia.

PURPOSE: We prospectively evaluated the ability of magnetic resonance imaging (MRI) of the thoraco-lumbar vertebrae to determine the relative amount of red and fatty marrow in children with aplastic anemia. PATIENTS AND METHODS: Twenty pediatric patients (ages 1-19 years) with aplastic anemia underwent T1-weighted (T1W, n = 31) and short T1 inversion recovery (STIR, n = 30) MRI of the midline sagittal thoraco-lumbar spine. Bone marrow (BM) biopsies from the posterior iliac crest (n = 29) were also performed. All studies were evaluated by blinded observers; MR grading was based on visual inspection of signal intensity. Biopsy-estimated cellularity was compared with T1W and STIR grading when these were performed within 14 days of each other (n = 16). All studies were compared to a simultaneous absolute neutrophil count (ANC), absolute reticulocyte count (ARC), and platelet count. RESULTS: BM cellularity estimated by BM biopsy was significantly associated with STIR grading (p = 0.032, Jonckheere-Terpstra test), as were peripheral ANC (p = 0.044), ARC (p = 0.007), and platelet count (p = 0.003). T1W grade was significantly associated with ANC (P = 0.011) but not ARC (p = 0.053) or platelet count (p = 0.377). Biopsy-estimated cellularity was associated with ANC (p = 0.032) and ARC (p = 0.036), but not platelet count (p = 0.282). CONCLUSION: In childhood aplastic anemia patients, STIR (and, to a lesser extent, T1W) MRI of the thoraco-lumbar spine reflects BM activity, as measured by peripheral blood ANC, ARC, and platelet count, and BM cellularity, as measured by BM biopsy. MRI may thus provide a noninvasive measure of hematopoietic status.

Age-related changes in proton T1 values of normal human brain.

To determine whether there were age-related changes in the brain tissue of 55 healthy adult volunteers (29 men, 26 women; 18-72 years old) without known brain abnormalities, a standard inversion-recovery technique was optimized for precise and accurate T1 measurement within the constraints of a 15-minute examination. Measurements of water proton T1 were obtained in eight brain regions. T1 increased with age in the genu (P < .001) (analysis of variance), frontal white matter (P < .05), occipital white matter (P < .05), putamen (P < .001), and thalamus (P << .001). A significant decrease in T1 with age was found in cortical gray matter (P < .05). Thus, age-related changes in T1 are present in a healthy population, even if extremes of age are excluded, suggesting that T1 values generally increase with age. However, increases in T1 were also observed in the genu, putamen, and thalamus of a substantial fraction of volunteers less than 35 years old. Aging healthy persons can show subtle, nonsymptomatic brain changes, suggesting that brain aging is associated with occult processes that can begin at a relatively early age.

Precise and accurate measurement of proton T1 in human brain in vivo: validation and preliminary clinical application.

Precise and accurate inversion-recovery (PAIR) magnetic resonance (MR) measurements of T1 were obtained in eight brain regions and cerebrospinal fluid of 26 healthy volunteers. Accuracy of the technique was assessed by measuring T1 in small fluid volumes with the PAIR technique and with two independent spectroscopic techniques. The mean difference between T1 measured with PAIR and with the two spectroscopic techniques was 3.1% +/- 1.3. The precision (reproducibility) of measurements with the PAIR technique was excellent. The coefficient of variation (CV) across 16 measurements in a head phantom was 2.0%, compared with a CV of 2.7% across 45 separate measurements in a single subject. The within-subject CV was 1.8% +/- 0.6 in white matter and 1.4% +/- 1.0 in basal ganglia. The between-subject CV in 26 healthy volunteers was 3.6% +/- 0.6 in white matter and 4.1% +/- 1.9 in basal ganglia. Comparison between a patient with an active recurrent brain tumor and an age-matched patient with an inactive brain tumor showed that T1 was significantly elevated throughout the brain of the active-tumor patient, especially in white matter tracts, even though no tumor or edema was detected in the white matter on standard MR images. Comparisons between five brain tumor patients and four healthy volunteers of similar age showed that T1 was significantly and substantially elevated throughout the white matter tracts and in the caudate nucleus, putamen, and thalamus. These results are consistent with the hypothesis that white matter tracts are selectively vulnerable to edema and that T1 increases in white matter are a sensitive indicator of patient status or tumor aggressiveness.

Discrete signal processing of dynamic contrast-enhanced MR imaging: statistical validation and preliminary clinical application.

A high-resolution image-based method was developed to analyze dynamic contrast agent-enhanced magnetic resonance images quantitatively. This method determines the initial rate of contrast agent accumulation, the delayed rate of accumulation, and the maximum enhancement in each pixel. These three parameters allow characterization of the dynamic signal features. Simulated noisy test sets of dynamic enhancement curves have shown this method to yield a fast and accurate characterization of the dynamic signal. Clinical examples of both qualitative image parameter maps and quantitative statistical analysis of the parameter distributions demonstrated the quality and potential of the technique. The technique is designed to yield imaging and quantitative information on contrast agent accumulation that can be useful in detecting residual tumor and evaluating response to therapy, while requiring less than 7 minutes of imaging time and 5 minutes of processing time per study.

Automated pixel-by-pixel mapping of dynamic contrast-enhanced MR images for evaluation of osteosarcoma response to chemotherapy: preliminary results.

An automated technique for pixel-by-pixel computer mapping of tumor necrosis was developed to improve the accuracy and applicability of dynamic contrast agent-enhanced magnetic resonance (MR) imaging in assessing the response of osteosarcoma to preoperative chemotherapy. The technique was evaluated in nine osteosarcoma patients who underwent MR imaging at diagnosis (n = 7) and after preoperative chemotherapy (n = 9). Sequential FLASH (fast low-angle shot) images of the tumor were obtained in one plane every 15 seconds before and for 3 minutes after gadopentetate dimeglumine injection. A region of interest was selected that included the entire tumor area. Slopes representing percent increase in signal intensity over baseline values per minute were calculated automatically for each pixel and displayed as gray-scale maps of the tumor. Matching histologic maps of each tumor were obtained. Visual region-by-region comparison of the pixel and histologic maps showed a high degree of correlation and the ability of the MR imaging technique to help identify small foci of residual viable tumor.

Primitive neuroectodermal tumors of the chest wall (Askin tumors): CT and MR findings.

OBJECTIVE: The objective of this study was to describe the CT and MR appearances of primitive neuroectodermal tumors of the thoracopulmonary region (Askin tumor), which typically manifest as large tumors involving the chest wall and pleura. This rare malignant neoplasm, seen predominantly in children and young adults, originates in soft tissues of the chest wall, occasionally in bone, or, rarely, in the periphery of the lung. SUBJECTS AND METHODS: The study group included two boys and six girls, 7-18 years old, with thoracic primitive neuroectodermal tumors who had had CT and MR studies at presentation. In seven of these patients, the preoperative imaging interpretation was compared with surgical observations. RESULTS: Seven tumors were large. Unilateral chest wall involvement was seen in all eight patients, pleural involvement in seven, and rib destruction in five. All tumors were heterogeneous on CT scans and T2-weighted MR images, and seven were heterogenous on T1-weighted MR images. The smallest tumor was homogeneous on T1-weighted MR images. Seven tumors had a signal intensity greater than that of skeletal muscle on T1-weighted MR images, and seven showed hemorrhage or necrosis. Invasion of muscle in the chest wall was noted on MR images in seven patients and on CT scans in four patients. CT scans and MR images showed extension of tumor into adjacent lung in four patients but were indeterminate in three patients. One patient had no extension of tumor into adjacent lung. Pulmonary metastases were noted on MR images in one patient and on CT scans in three patients. CT and MR studies correctly showed pleural (n = 6), rib (n = 4), pericardial (n = 1), diaphragmatic (n = 1), and vertebral/spinal cord (n = 1) involvement, confirmed during surgery. CT and MR scans of five patients imaged before surgery were indeterminate for adjacent lung invasion. CONCLUSION: The described radiologic features of Askin tumors may be useful in deciding when to include this entity in the differential diagnosis. Areas of hemorrhage and necrosis in the large tumors are responsible for their heterogeneous appearance on CT scans and MR images. CT scans and MR images are complementary for determining the extent of disease. MR imaging is informative for determining invasion of chest wall muscle, whereas CT scanning is preferred for detecting small pulmonary metastases. Neither technique is adequate for predicting invasion of adjacent lung.

Vaginal occlusion induced by cancer therapy.

Two adolescent girls with acquired vaginal occlusion and resultant hematometracolpos are presented. Both are long-term survivors of childhood malignancies, who prior to multiagent chemotherapy and pelvic irradiation had normal uteri by imaging. Both were amenorrheic post therapy. Routine follow-up computed tomography (CT) scans to monitor their malignancies demonstrated unexpected cystic pelvic masses, subsequently diagnosed as hematometracolpos.

Pediatric musculoskeletal tumors: use of dynamic, contrast-enhanced MR imaging to monitor response to chemotherapy.

The ability of dynamic, gadolinium-enhanced magnetic resonance (MR) imaging to allow prediction of histologic responses to initial chemotherapy was evaluated in 20 patients with osteosarcoma (n = 12), Ewing sarcoma (n = 4), rhabdomyosarcoma (n = 3), or synovial sarcoma (n = 1). Tumor signal intensity was measured on fast low-angle shot (FLASH) gradient-echo images obtained at 15-second intervals before and 3 or more minutes after manual intravenous injection of gadopentetate dimeglumine. Signal intensity was plotted against time, and slopes were calculated for the percentage increase in signal intensity per minute. Slopes and changes in maximum tumor size during and after chemotherapy were correlated with histologic evaluations of tumor response. Eleven of the 20 tumors met histologic criteria for response. Histologic response was moderately correlated with slopes obtained during chemotherapy (rs [Spearman rank correlation] = .53, P = .02) but not with changes in tumor size (rs = .02, P = .94). Tumor slopes obtained after chemotherapy were highly correlated with histologic findings (rs = .65, P = .007); the correlation with changes in tumor size increased but remained nonsignificant (rs = .41, P = .11).

MR imaging detection of calcified intracranial lesions and differentiation from iron-laden lesions.

Magnetic susceptibility variation caused by calcium permits limited detection of intracranial calcifications and/or their distinction from iron-laden lesions with spin-echo or gradient-echo magnetic resonance (MR) techniques. The magnetic susceptibility sensitivity of phase imaging has been used to detect iron-laden lesions. A new approach that combines the magnetic susceptibility sensitivity of both gradient-echo and phase imaging to yield greater imaging sensitivity to calcium is presented. Two-dimensional fast low-angle shot (FLASH) gradient-echo imaging with phase image reconstruction (gradient-echo phase [GEP]) was used at 1.0 and 1.5 T. Twelve patients with computed tomography-proved calcified intracranial lesions (greater than or equal to 200 HU) and seven patients with iron-laden intracranial lesions having a characteristic appearance on T1- and T2-weighted and FLASH MR images were studied. The GEP imaging technique helped detect calcified intracranial lesions (greater than or equal to 200 HU) and helped distinguish them from iron-laden lesions.