Predictive and diagnostic measures for kernicterus spectrum disorder: a prospective cohort study.

BACKGROUND: Kernicterus spectrum disorder (KSD) resulting from neonatal hyperbilirubinemia remains a common cause of cerebral palsy worldwide. This 12-month prospective cohort study followed neonates with hyperbilirubinemia to determine which clinical measures best predict KSD. METHODS: The study enrolled neonates ≥35 weeks gestation with total serum bilirubin (TSB) ≥ 20 mg/dl admitted to Aminu Kano Hospital, Nigeria. Clinical measures included brain MRI, TSB, modified bilirubin-induced neurologic dysfunction (BIND-M), Barry-Albright Dystonia scale (BAD), auditory brainstem response (ABR), and the modified KSD toolkit. MRI signal alteration of the globus pallidus was scored using the Hyperbilirubinemia Imaging Rating Tool (HIRT). RESULTS: Of 25 neonates enrolled, 13/25 completed 12-month follow-up and six developed KSD. Neonatal BIND-M ≥ 3 was 100% sensitive and 83% specific for KSD. Neonatal ABR was 83% specific and sensitive for KSD. Neonatal HIRT score of 2 was 67% sensitive and 75% specific for KSD; this increased to 100% specificity and sensitivity at 12 months. BAD ≥ 2 was 100% specific for KSD at 3-12 months, with 50-100% sensitivity. CONCLUSIONS: Neonatal MRIs do not reliably predict KSD. BIND-M is an excellent screening tool for KSD, while the BAD or HIRT score at 3 or 12 months can confirm KSD, allowing for early diagnosis and intervention. IMPACT: The first prospective study of children with acute bilirubin encephalopathy evaluating brain MRI findings over the first year of life. Neonatal MRI is not a reliable predictor of kernicterus spectrum disorders (KSD). Brain MRI at 3 or 12 months can confirm KSD. The modified BIND scale obtained at admission for neonatal hyperbilirubinemia is a valuable screening tool to assess risk for developing KSD. The Barry Albright Dystonia scale and brain MRI can be used to establish a diagnosis of KSD in at-risk infants as early as 3 months.

Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation.

INTRODUCTION: MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms. METHODS AND ANALYSIS: Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation-thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans. ETHICS AND DISSEMINATION: IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor. TRIAL REGISTRATION NUMBER: NCT02811263; Pre-result.

3T magnetic resonance imaging accurately depicts radiofrequency ablation zones in a blood-perfused bovine liver model.

PURPOSE: To determine if noncontrast T1-weighted (T1W) images from 3T magnetic resonance (MR) imaging accurately depict radiofrequency (RF) ablation zones as determined macroscopically and microscopically in a blood-perfused bovine liver model. MATERIALS AND METHODS: Three-dimensional (3D) gradient-recalled echo (GRE) T1W images were obtained on a 3T MR imaging scanner after RF ablations (n = 14) of in vitro blood-perfused bovine livers. The resulting central hypointense and peripheral hyperintense signal regions were measured and compared with the inner tan and outer red zones of the gross specimen. Corresponding ablated hepatic tissue samples were examined microscopically and stained with nicotinamide adenine dinucleotide phosphate (NADPH) to assess for the presence or absence of NADPH diaphorase activity. Bootstrap two-sample hypothesis tests were used to compare MR imaging, gross, and histopathologic measurements. RESULTS: The MR imaging inner ablation zone had a mean radius of 0.80 cm (range 0.33-1.14 cm); the inner zone plus the outer ablation zone had a mean radius of 1.40 cm (range 1.01-1.74 cm). Comparison of the measurements of the inner ablation zone on MR imaging versus the gross specimen showed equivalence (95% confidence interval [CI] -0.122 cm, 0.223 cm). Comparison of the measurements of the outer ablation zone on MR imaging versus the gross and histologic specimens also showed equivalence (95% CI -0.095 cm, 0.244 cm, and -0.146 cm, 0.142 cm). CONCLUSIONS: Noncontrast 3D GRE T1W 3T MR imaging accurately depicts the RF ablation zones in a blood-perfused bovine liver model and can be used as a noninvasive means to assess the 3D morphologic characteristics of RF ablation lesions in the model.

In vitro blood-perfused bovine liver model: a physiologic model for evaluation of the performance of radiofrequency ablation devices.

PURPOSE: To describe an in vitro blood-perfused bovine liver model for the testing of radiofrequency (RF) ablation devices and compare the performance of a specific RF ablation device in the model relative to three other biologic models. MATERIALS AND METHODS: Fresh bovine livers were used to create three in vitro models: blood-perfused, Krebs-Henseleit (KH) solution-perfused, and nonperfused. The perfused models were connected to a heart-lung machine via the portal vein and perfused with heparinized autologous blood or KH solution under physiologic conditions. Six swine were used as in vivo liver models. A cluster electrode and RF ablation system was operated in impedance mode for 12 minutes in all models. Ablated livers were sectioned, with long- and short-axis measurements of the ablations obtained, and statistical analysis was performed. RESULTS: A total of 39, 23, 17, and 12 ablations were performed in 14, 6, 5, and 6 blood-perfused bovine livers, KH solution-perfused bovine livers, nonperfused bovine livers, and in vivo porcine livers, respectively. On cut specimens, the average diameters of ablation zones were 4.00 cm (95% CI, 3.88-4.13) in blood-perfused livers, 4.34 cm (95% CI, 4.14-4.50) in KH solution-perfused livers, 4.67 cm (95% CI, 4.50-4.83) in nonperfused livers, and 3.56 cm (95% CI, 3.26-3.83) in in vivo porcine livers. In all models, the ablation zone diameters were normally distributed. CONCLUSIONS: In the in vitro blood-perfused bovine liver model, the size of ablations produced by an RF ablation device are closer in size to those seen in porcine liver in vivo compared with the lesions produced in KH solution-perfused or nonperfused bovine liver.

Combination radiofrequency ablation and intravenous radiolabeled liposomal Doxorubicin: imaging and quantification of increased drug delivery to tumors.

PURPOSE: To identify, with noninvasive imaging, the zone of radiopharmaceutical uptake after combination therapy with radiofrequency (RF) ablation and intravenous administration of technetium 99m ((99m)Tc) liposomal doxorubicin in a small-animal tumor model, and to quantify and correlate the uptake by using imaging and tissue counting of intratumoral doxorubicin accumulation. MATERIALS AND METHODS: This study was approved by the animal care committee. Two phases of animal experiments were performed. In the first experiment, a single human head-and-neck squamous cell carcinoma tumor was grown in each of 10 male nude rats. Seven of these animals were treated with intravenous (99m)Tc-liposomal doxorubicin followed by RF tumor ablation at a mean temperature of 70 degrees C + or - 2 for 5 minutes, and three were treated with intravenous (99m)Tc-liposomal doxorubicin only. Combination single photon emission computed tomography-computed tomography (SPECT/CT) was performed at 15 minutes, 4 hours, and 20 hours after therapy. In the second experiment, two tumors each were grown in 11 rats, but only one of the tumors was ablated after intravenous administration of (99m)Tc-liposomal doxorubicin. SPECT/CT and planar scintigraphy were performed at the same posttreatment intervals applied in the first experiment, with additional planar imaging performed at 44 hours. After imaging, tissue counting in the excised tumors was performed. Radiotracer uptake, as determined with imaging and tissue counting, was quantified and compared. In a subset of three animals, intratumoral doxorubicin accumulation was determined with fluorimetry and correlated with the imaging and tissue-counting data. RESULTS: At both SPECT/CT and planar scintigraphy, increased uptake of (99m)Tc-liposomal doxorubicin was visibly apparent in the ablated tumors. Results of quantitative analysis with both imaging and tissue counting confirmed significantly greater uptake in the RF ablation-treated tumors (P < .001). Intratumoral doxorubicin accumulation correlated closely with imaging (r = 0.9185-0.9871) and tissue-counting (r = 0.995) results. CONCLUSION: Study results show that increased delivery of intravenous liposomal doxorubicin to tumors combined with RF ablation can be depicted and quantified with noninvasive imaging.

Percutaneous radiofrequency ablation of hepatic tumors against the diaphragm: frequency of diaphragmatic injury.

PURPOSE: To retrospectively determine the frequency of diaphragmatic injury when percutaneous hepatic radiofrequency (RF) ablation is performed adjacent to the diaphragm. MATERIALS AND METHODS: Institutional Review Board approval was obtained for our HIPAA-compliant study. Informed consent for the ablation procedure and for use of related data for future research was obtained from each patient. A retrospective review was conducted of 215 patients undergoing percutaneous RF ablation of hepatic tumors. Twenty-nine patients (21 men and eight women; age, 41-89 years) were identified with tumors abutting the diaphragm. Episodes of right shoulder pain were recorded. A panel of radiologists blinded to the patients' clinical histories reviewed their imaging for evidence of diaphragmatic injury and ablation success. A generalized estimating equation model and the Fisher exact test were used for statistical analysis. RESULTS: The 29 patients had a total of 33 tumors abutting the diaphragm. Tumor size was 1.3-5.5 cm (mean, 3.2 cm +/- 1.1). After ablation, five (17%) patients reported right shoulder pain. In four, pain was mild or moderate, with symptoms lasting 2-14 days (median, 5.5 days). Three of these showed diaphragmatic thickening on postablation computed tomographic (CT) scans. One patient had severe pain lasting 2 weeks, followed by milder pain for 2 months. This patient's postablation CT images showed focal nodular diaphragmatic thickening. This patient was treated with a multitined device; the other four, with straight-needle devices. Local tumor progression was seen in 14 tumors (42.4%). Tumors 3 cm or smaller had a much lower local progression rate than tumors larger than 3 cm (12.5% vs 70.6%). CONCLUSION: Of 29 patients who had ablation of hepatic tumors adjacent to the diaphragm, five (17%) had diaphragmatic injury, which was clinically apparent with right shoulder pain.

Thermal ablation for hepatocellular carcinoma.

Thermal ablation, as a form of minimally invasive therapy for hepatocellular carcinoma (HCC), has become an important treatment modality. Because of the limitations of surgery, the techniques of thermal ablation have become standard therapies for HCC in some situations. This article reviews 4 thermal ablation techniques-radiofrequency (RF) ablation, microwave ablation, laser ablation, and cryoablation. Each of these techniques may have a role in treating HCC, and the mechanisms, equipment, patient selection, results, and complications of each are considered. Furthermore, combined therapies consisting of thermal ablation and adjuvant chemotherapy also show promise for enhancing these techniques. Important areas of research into thermal ablation remain, including improving the ability of ablation to treat larger tumors, determining the indications for each thermal ablation modality, optimizing image guidance, and obtaining good outcome data on the efficacy of these techniques.