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Purpose: Cerebral T 2 oximetry is a non-invasive imaging method to measure blood T 2 and cerebral venous oxygenation. Measured T 2 values are converted to oximetry estimates using carefully validated and potentially disease-specific calibrations. In sickle cell disease, red blood cells have abnormal cell shape and membrane properties that alter T 2 oximetry calibration relationships in clinically meaningful ways. Previous in vitro works by two independent groups established potentially competing calibration models., Methods: This study analyzed pooled datasets from these two studies to establish a unified and more robust sickle-specific calibration to serve as a reference standard in the field., Results: Even though the combined calibration did not demonstrate statistical superiority compared to previous models, the calibration was unbiased compared to blood-gas co-oximetry and yielded limits of agreement of (-10.1%, 11.6%) in non-transfused subjects with sickle cell disease. In transfused patients, this study proposed a simple correction method based on individual hemoglobin S percentage that demonstrated reduced bias in saturation measurement compared to previous uncorrected sickle calibrations., Conclusion: The combined calibration is based on a larger range of hematocrit, providing greater confidence in the hematocrit-dependent model parameters, and yielded unbiased estimates to blood-gas co-oximetry measurements from both sites. Additionally, this work also demonstrated the need to correct for transfusion in T 2 oximetry measurements for hyper-transfused sickle cell disease patients and proposes a correction method based on patient-specific hemoglobin S concentration., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: T 2 MRI oximetry can noninvasively determine oxygen saturation (Y) but requires empirical MR calibration models to convert the measured blood transverse relaxation (T 2b ) into Y. The accuracy of existing T 2b models in the presence of blood disorders such as sickle cell disease (SCD) remains unknown., Methods: A Carr Purcell Meiboom Gill T 2 preparation sequence was used to make 83 whole blood measurements from 11 subjects with SCD to derive an ex vivo sickle hemoglobin (HbS) T 2b model. Forearm venous blood gas, sagittal sinus T 2 (T 2 Relaxation Under Spin Tagging) and total brain blood flow (phase contrast MRI) were measured in 37 healthy controls and 33 SCD subjects (age 24.6 ± 10.2 years). Cerebral oxygen saturation, extraction fraction, and metabolic rate estimates were calculated using three separate T 2b models. Cerebral and forearm oxygen extraction fraction were compared., Results: Ex vivo, SCD blood had greater saturation dependent relaxivity than control blood, with a weak dependence on HbS and no dependence on hematocrit. In vivo, the HbS T 2b model predicted Y v values with lowest coefficient of variation (compared with existing T 2b models) and the strongest correlation with peripheral venous oximetry (r 2  = .29). The HbS T 2b model predicted systematically higher Y v measurements in SCD patients (73 ± 5 and 61 ± 6; P < 0.0001) which was mirrored by peripheral venous measurements (75 ± 20 and 45 ± 20; P < 0.0001)., Conclusion: Cerebral and peripheral oxygen extraction are decreased in SCD patients, suggesting either blood flow is increased beyond metabolic demands or the presence of physiological arterial-venous shunting. Magn Reson Med 80:294-303, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Iron-induced cardiac dysfunction is a leading cause of death in transfusion-dependent anemia. MRI relaxation rates R2(1/T2) and R2*(1/T2*) accurately predict liver iron concentration, but their ability to predict cardiac iron has been challenged by some investigators. Studies in animal models support similar R2 and R2* behavior with heart and liver iron, but human studies are lacking. To determine the relationship between MRI relaxivities and cardiac iron, regional variations in R2 and R2* were compared with iron distribution in one freshly deceased, unfixed, iron-loaded heart. R2 and R2* were proportionally related to regional iron concentrations and highly concordant with one another within the interventricular septum. A comparison of postmortem and in vitro measurements supports the notion that cardiac R2* should be assessed in the septum rather than the whole heart. These data, along with measurements from controls, provide bounds on MRI-iron calibration curves in human heart and further support the clinical use of cardiac MRI in iron-overload syndromes., (Copyright (c) 2006 Wiley-Liss, Inc.)

MRI is becoming an increasingly important tool to assess iron overload disorders, but the complex nature of proton-iron interactions has troubled noninvasive iron quantification. Intersite and intersequence variability as well as methodological inaccuracies have been limiting factors to its widespread clinical use. It is important to understand the underlying proton relaxation mechanisms within the (human) tissue environment to address these differences. In this respect, NMR relaxometry was performed on 10 fresh human liver biopsy specimens taken from patients with transfusion-dependent anemia. T1 (1/R1) inversion recovery, T2 (1/R2) single echo, and multiecho T2 CPMG measurements were performed on a 60-MHz Bruker Minispectrometer. NMR parameters were compared to quantitative iron levels and tissue histology. Relaxivities R1 and R2 both increased linearly with hepatic iron content, with R2 being more sensitive to iron. CPMG data were well described by a chemical-exchange model and predicted effective iron center dimensions consistent with hemosiderin-filled lysosomes. Nonexponential relaxation was evident at short refocusing intervals with R2 and amplitude behavior suggestive of magnetic susceptibility-based compartmentalization rather than anatomic subdivisions. NMR relaxometry of human liver biopsy specimens yields unique insights into the mechanisms of tissue-iron relaxivity., ((c) 2005 Wiley-Liss, Inc.)

Benefits and risks of nutrition support were evaluated in 31 malnourished children with newly diagnosed Wilms' tumor managed according to the third National Wilms' Tumor Study protocol. Patients were classified at diagnosis as being at high nutritional risk (HNR, n = 19) or low nutritional risk (LNR, n = 12). Ten HNR patients were randomized to central parenteral nutrition (CPN) and nine HNR patients were randomized to peripheral parenteral nutrition (PPN) plus enteral nutrition (EN) for 4 weeks of initial intense treatment and EN (nutritional counseling, oral foods and supplements) thereafter. Thirteen HNR patients (seven CPN, six PPN) completed the protocol. Twelve LNR patients received EN; 11 Stage I malnourished patients were randomized to 10 or 26 weeks of chemotherapy. Dietary, anthropometric, and biochemical data were determined for HNR patients at weeks 0-4, 6, 13, 19, and 26 and for LNR patients at weeks 1, 2, 5, and 26. In HNR patients, adequate parenteral nutrition support reversed protein energy malnutrition (PEM), and prevented chemotherapy and radiotherapy delays due to granulocytopenia. CPN was superior to PPN in reversing PEM: energy intake, weight gain, and retinol binding protein were higher (P less than 0.05). LNR patients lost weight and fat reserves in the first 2 weeks of treatment; depletion persisted at week 5, and 25% had chemotherapy delays. Thereafter, EN reversed PEM in patients with both chemotherapy regimens. These data suggest that CPN is preferable during initial intense treatment for HNR patients, and that, although EN is ineffective in preventing depletion and treatment delays in the first 5 weeks of treatment for LNR patients, it is effective thereafter.

The effectiveness of enteral and parenteral nutrition regimens in preventing or reversing protein-energy malnutrition (PEM) and in preventing treatment delays was evaluated in 32 children receiving treatment for newly diagnosed Stage III (3 patients) and IV (29 patients) neuroblastoma. Ten of 18 malnourished patients were randomized to central parenteral nutrition (CPN) and 8 to peripheral parenteral nutrition (PPN) plus enteral nutrition for 4 weeks and then received enteral nutrition (EN: intense nutrition counselling, oral foods and supplements) for weeks 5 through 10. Ten of 14 nourished patients received EN and 4 CPN for 4 weeks and EN thereafter. Dietary, anthropometric and biochemical measurements were determined for weeks 0, 1, 2, 3, 4, 7, and 10 for 24 patients who completed the protocols. In malnourished patients, both CPN (seven patients) and PPN (seven patients) were effective in reversing PEM in the first 4 weeks; thereafter, EN effectively maintained nutritional gains in both groups. In nourished patients, EN (seven patients) was not as effective as CPN (three patients) in preventing PEM during the first 4 weeks; afterwards, EN maintained gains in the CPN group but did not promote needed increases in weight nor fat reserves in the EN group. Patients supported by parenteral nutrition (PN, weeks 1-4) had fewer treatment delays (2/17, 12%) than EN patients (4/7, 57%, P less than 0.05). These data indicate that PN reverses or prevents PEM and prevents treatment delays during the first 4 weeks of intense oncologic treatment and provides nutritional benefits which can be maintained with EN thereafter.

A positive stance towards nutrition support of the child with cancer assures potential for normal growth, development, and quality of life during extended oncologic treatment. Data from recent studies of children with cancer (advanced neuroblastoma, Wilms' tumor) demonstrate the importance of integrating nutrition staging, assessment, and support into treatment protocols. Patients with solid tumors and lymphomas who are malnourished at diagnosis have a poor outcome when compared to nourished counterparts. Enteral nutrition (intensive nutrition counseling and favorite, nutritious foods) is effective in low nutritional risk groups but ineffective in preventing or reversing protein-energy malnutrition in high nutritional risk groups. For high-risk groups, central parenteral nutrition is a relatively short-term, but important, support measure which allows children to grow despite extended periods of intense oncologic treatment. The patient's nutritional course may affect bone marrow suppression and the ability to tolerate aggressive chemotherapeutic treatment. Although treatment tolerance may be improved with nutrition support, adequacy of primary oncologic treatment outweighs other supportive factors as a determinant of ultimate survival.

The short-term and long-term effectiveness of central parenteral nutrition (CPN) versus peripheral parenteral nutrition (PPN) in improving muscle mass (arm muscle area [AMA]) was evaluated for 24 malnourished children with newly diagnosed Stage IV neuroblastoma (n = 14) or Stages II-V Wilms' tumor (n = 10). Patients were randomized to either CPN or PPN plus enteral nutrition (EN: intense nutrition counseling, oral foods, and supplements) for 4 weeks followed by EN until week 10. Oncologic treatment was similar for each tumor type. Dietary, anthropometric, and biochemical measurements were obtained at weeks 0, 4, and 10. During weeks 1 through 4, energy (CPN: means 100 +/- 4; PPN: means 96 +/- 4% of healthy children) and protein (CPN: means 2.5 +/- 0.1; PPN means 2.7 +/- 0.2 g/kg) intakes of the two groups did not differ. The AMA increased (P less than 0.05) with 4 weeks of CPN but not with PPN; changes thereafter with EN were not significant. Weight (P less than 0.05) and triceps skinfolds (P less than 0.01) increased with 4 weeks of PN in both groups and decreased with EN thereafter (P less than 0.01) but were higher at week 10 than diagnosis. Increases in albumin in both groups reached significance at week 10 (P less than 0.05). These data show that CPN improves AMA in malnourished children with neuroblastoma or Wilms' tumor when energy and protein intakes are adequate. The AMA gains can be maintained thereafter with EN.

Sudden cerebrovascular insults occurred during or immediately following remission induction therapy in 4 children with acute lymphoblastic leukemia. In 3, cerebral infarction was due to thrombosis. In the fourth, an intracerebral hematoma developed representing either frank hemorrhaging or a hemorrhagic infarction. None of the patients had central nervous system leukemia or extreme leukocytosis at the time of diagnosis. Symptoms were obtundation, hemiparesis, seizures, and headache. The induction chemotherapy included L-asparaginase which causes deficiencies of antithrombin, plasminogen, fibrinogen, and factors IX and XI. These hemostatic abnormalities may explain the thromboses and bleeding observed in these children.

The effect of the state of nutrition of 18 children with Stage IV neuroblastoma at diagnosis and during initial therapy, was evaluated with respect to treatment delays, drug dosage alterations, tumor response, days to first event (relapse or death), and survival. All patients received similar therapy (CCSG protocol CCG 371). Based on nutrition staging at diagnosis, nine were classified as malnourished; four were randomized to receive total parenteral nutrition (TPN) and four peripheral parenteral nutrition plus enteral nutrition for 28 days (through 2 chemotherapy courses), and one died before randomization. Nine were nourished at diagnosis; seven received a comprehensive enteral nutrition program and two received TPN. By life-table analysis, the duration of remission was significantly greater in the nourished than the malnourished (P less than 0.01) and a trend towards improved survival was evident at one year (P = 0.08). The median length of survival for children nourished at diagnosis was approximately 12 months, whereas those malnourished had a median survival of only 5 months. Nine children remained nourished or were becoming renourished during the first 21 days of therapy, and one of these had treatment delays and decreased drug dosages. Seven were becoming malnourished or remained malnourished during this period and six had treatment delays (P less than 0.01). These data support the idea that nutrition staging at diagnosis and during initial treatment should be an integral part of protocol design and initial evaluation of children with Stage IV neuroblastoma.