Effects of photobiomodulation and caffeine treatment on acute kidney injury in a hypoxic ischemic neonatal rat model.

Hypoxic ischemic encephalopathy (HIE) occurs in 2-5/1000 births, with acute kidney injury (AKI) occurring in 40%. AKI increases morbidity and mortality. Caffeine, an adenosine receptor antagonist, and photobiomodulation (PBM), working on cytochrome c oxidase, are potential treatments for AKI. To examine effects of caffeine and PBM on AKI in rats, Day 7 pups underwent a HIE intervention (Modified Rice-Vannucci model) replicating pathology observed in humans. Caffeine was administered for 3 days and/or PBM for 5 days following HIE. Weights and urine for biomarkers (NGAL, albumin, KIM-1, osteopontin) were collected prior to HIE, daily post intervention and at sacrifice. Both treatments reduced kidney injury seen on electron microscopy, but not when combined. HIE elevated urinary NGAL and albumin on Days 1-3 post-HIE, before returning to control levels. This elevation was significantly reduced by PBM or caffeine. KIM-1 was significantly elevated for 7 days post-HIE and was reduced by both treatments. Osteopontin was not altered by HIE or the treatments. Treatments, individually but not in combination, improved HIE-induced reductions in the enzymatic activity of mitochondrial complexes II-III. PBM and caffeine also improved weight gain. PBM and caffeine reduces AKI diagnosed by urinary biomarkers and confirmed by EM findings.

CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non-hodgkin's lymphomas.

OBJECTIVES: The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). METHODS: This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10-62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. RESULTS: A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre-treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre-treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CONCLUSION: CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL. KEY POINTS: • CT texture-analysis (CTTA) provides prognostic information complementary to interim FDG-PET in Lymphoma. • Pre-treatment CTTA and interim PET status were significant predictors of progression-free survival. • Patients with negative interim PET could be further stratified by pre-treatment CTTA. • Provide precision surveillance where additional imaging reserved for patients at greatest recurrence-risk. • Assists in risk-adapted treatment strategy based on interim PET and CTTA.

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules-the SPUtNIk study.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently. METHODS AND ANALYSIS: The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) (18FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for 18FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs. ETHICS AND DISSEMINATION: Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN30784948; Pre-results.

A comparison of the psychological burden of PET/MRI and PET/CT scans and association to initial state anxiety and previous imaging experiences.

OBJECTIVE: To investigate the level of psychological burden experienced by patients undergoing positron emission tomography (PET)/MRI scanning compared with PET/CT. METHODS: 100 adult patients referred for PET/CT and underwent PET/MRI scanning were eligible. Initial state, psychological burden of PET/CT and PET/MRI, scan satisfaction and preference were assessed using a purpose-designed questionnaire, comprising 61 five-point Likert scale questions and a three-point tick box question indicating preference between PET/CT and PET/MRI. State anxiety was assessed using the state portion of the State Trait Anxiety Inventory. Wilcoxon signed-rank tests compared psychological burden experienced by participants following PET/CT and PET/MRI scan. RESULTS: A greater level of psychological burden was experienced by patients during PET/MRI than PET/CT p ≤ 0.001, consistent with patients' preference for PET/CT over PET/MRI (p = 0.013). There was a significant relationship between PET/CT psychological burden and initial state (r = 0.386, p ≤ 0.001). No significant relationship was identified between Initial state and psychological burden of PET MRI (r = -0.089; p = 217). There was a significant relationship between psychological burden of PET/CT and PET/MRI (r = 0.354; p = 0.001). CONCLUSION: Patients' experience increased psychological burden during PET/MRI compared with PET/CT. Previous scanning experiences and patients' interactions prior to and during PET/MRI improved patient satisfaction. Interventions could be implemented to improve imaging outcome. ADVANCES IN KNOWLEDGE: This study provides evidence for the increased psychological burden of PET/MRI compared with PET/CT, and that people prefer the PET/CT procedure. We have shown that the patients who expressed a preference for PET/MRI demonstrated significantly lower psychological burden for that procedure than those that preferred PET/CT, which indicates that the benefit of reduced psychological burden could be facilitated by an appropriate intervention.

Computer-controlled stimulation for functional magnetic resonance imaging studies of the neonatal olfactory system.

AIM: Olfactory sensation is highly functional early in human neonatal life, with studies suggesting that odours can influence behaviour and infant-mother bonding. Due to its good spatial properties, blood oxygen level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) has the potential to rapidly advance our understanding of the neural activity which underlies the development of olfactory perception in this key period. We aimed to design an 'olfactometer' specifically for use with neonatal subjects for fMRI studies of odour perception. METHODS: We describe a fully automated and programmable, fMRI compatible system capable of presenting odorant liquids. To prevent contamination of the system and minimize between-subject infective risk, the majority of the olfactometer is constructed from single-use, readily available clinical equipment. The system was used to present the odour of infant formula milk in a validation group of seven neonatal subjects at term equivalent postmenstrual age (median age 40 weeks). RESULTS: A safe, reliable and reproducible pattern of stimulation was delivered leading to well-localized positive BOLD functional responses in the piriform cortex, amygdala, thalamus, insular cortex and cerebellum. CONCLUSIONS: The described system is therefore suitable for detailed studies of the ontology of olfactory sensation and perception during early human brain development.

Can upright myocardial perfusion imaging be used alone with a solid-state dedicated cardiac camera?

AIM: The novel solid state dedicated cardiac cameras provide fast high resolution cardiac imaging. The D-SPECT camera enables semi-reclining (upright) positioning, increasing comfort and potentially reducing movement during myocardial perfusion imaging. Physicians are generally familiar with supine imaging and the different positioning in upright imaging could potentially cause diagnostic challenges. The aim of this study was to compare the upright and supine imaging for diagnostic ability to assess Physician confidence and determine any artefacts in upright imaging. METHODS: Fifty-five patients underwent myocardial perfusion imaging on the D-SPECT camera in both upright and supine positions. Where both images showed the same defects the 2 techniques were regarded as equally diagnostic. Where only one set showed a defect this was regarded as artefact and was defined as non-diagnostic. The location and cause of the artefact was recorded. RESULTS: In 13 /55 patients either form of imaging was regarded as equally diagnostic. In 24/55 the supine images revealed artefact affecting interpretation. The reasons for this were most frequently large BMI, motion and gut uptake. In 18/55 upright images were considered non-diagnostic. In 16/18 this was due to an infero-apical defect seen in female patients (14/16) with raised BMI and/or large breasts. CONCLUSION: Upright myocardial perfusion imaging on D-SPECT shows a common artefact (in up to 1/3 of cases) in the infero-apical region mainly in overweight female patients. Getting acquainted with this artefact this may increase Physician confidence in reporting, similarly as to conventional supine imaging. Indeed, some of the artefacts seen on supine imaging appear less commonly with upright imaging. Thus, upright imaging can potentially be used alone for diagnosis with D-SPECT. Performance of both supine and upright imaging can be reserved for overweight patients thereby minimizing impact on scanning time and clinical throughput in busy departments.

Current status and guidelines for the assessment of tumour vascular support with dynamic contrast-enhanced computed tomography.

Dynamic contrast-enhanced computed tomography (DCE-CT) assesses the vascular support of tumours through analysis of temporal changes in attenuation in blood vessels and tissues during a rapid series of images acquired with intravenous administration of iodinated contrast material. Commercial software for DCE-CT analysis allows pixel-by-pixel calculation of a range of validated physiological parameters and depiction as parametric maps. Clinical studies support the use of DCE-CT parameters as surrogates for physiological and molecular processes underlying tumour angiogenesis. DCE-CT has been used to provide biomarkers of drug action in early phase trials for the treatment of a range of cancers. DCE-CT can be appended to current imaging assessments of tumour response with the benefits of wide availability and low cost. This paper sets out guidelines for the use of DCE-CT in assessing tumour vascular support that were developed using a Delphi process. Recommendations encompass CT system requirements and quality assurance, radiation dosimetry, patient preparation, administration of contrast material, CT acquisition parameters, terminology and units, data processing and reporting. DCE-CT has reached technical maturity for use in therapeutic trials in oncology. The development of these consensus guidelines may promote broader application of DCE-CT for the evaluation of tumour vascularity. Key Points • DCE-CT can robustly assess tumour vascular support • DCE-CT has reached technical maturity for use in therapeutic trials in oncology • This paper presents consensus guidelines for using DCE-CT in assessing tumour vascularity.

Increased metabolic activity in abdominal aortic aneurysm detected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT).

OBJECTIVES: Abdominal aortic aneurysms (AAAs) are associated with an inflammatory cell infiltrate and enzymatic degradation of the vessel wall. The aim of this study was to detect increased metabolic activity in the wall of the AAA with 18F-fluorodeoxyglucose ((18)F-FDG), mediated by glucose transporter protein (GLUTs), using a dedicated hybrid PET/64-detector CT. DESIGN, METHOD AND MATERIALS: 14 patients (All male, mean age 73.6 years, range 61-82) with AAA under surveillance underwent PET/CT scanning with 175 MBq of intravenous (18)F-FDG. The maximum aneurysm diameter and calcification score were determined on the attenuation correction CT. A volume of interest was placed on the aneurysm sac and the maximum Standardised Uptake Value (SUV(max)) measured. RESULTS: The mean aneurysm diameter was 5.4 cm (SD+/-0.8). Two aneurysms had the CT characteristics of inflammatory aneurysms. Twelve aneurysms showed increased FDG uptake (SUV(max)>2.5). There was no significant difference in FDG uptake between heavily calcified aneurysms and non-heavily calcified aneurysms (t-test). There was a significant increase in the FDG uptake in the two inflammatory aneurysms compared to the other twelve aneurysms (t-test; P=0.04). CONCLUSION: The findings in this study offer in vivo evidence that the AAA wall shows increased glucose metabolism, mediated by the GLUTs: this increased metabolic activity as detected by PET/CT may be present in most AAAs.

Echocardiographic assessment of blood flow volume in the superior vena cava and descending aorta in the newborn infant.

BACKGROUND: Clinical methods of assessing adequacy of the circulation are poor predictors of volume of blood flow in the newborn preterm. Doppler echocardiography can be used to assess perfusion at various sites in the circulation. OBJECTIVE: To assess repeatability of measurement of volume of superior vena caval (SVC) and descending aortic (DAo) flow. DESIGN: SVC and DAo flow volume were assessed four times in the first 48 h of postnatal life in a cohort of preterm (<31 weeks) infants. Within-observer and between-observer repeatability was assessed in a subgroup of preterm infants. Normative values were derived from 14 preterm infants who required <48 h respiratory support and 13 healthy term infants. RESULTS: Within-observer repeatability coefficient was 30 ml/kg/min for quantification of SVC flow, and 2.2 cm for DAo stroke distance. Measurement of DAo diameter had poor repeatability. Between-observer repeatability appeared poorer than within-observer repeatability. The fifth centile for volume of SVC flow in healthy preterm infants was 55 ml/kg/min and 4.5 cm for DAo stroke distance. CONCLUSIONS: Echocardiographic assessments of volume of SVC flow and velocity of DAo flow have similar within-observer repeatability to other neonatal haemodynamic measurements. Between-observer repeatability for both measurements was poor, reflecting the difficulty of standardising these novel techniques. In this small cohort of preterm infants, SVC flow volume <55 ml/kg/min and DAo stroke distance <4.5 cm represented low or borderline systemic perfusion in the first 48 h of postnatal life.

Relationship between blood pressure and blood flow in newborn preterm infants.

BACKGROUND: Arterial blood pressure remains the most frequently monitored indicator of neonatal circulatory status. However, studies of systemic perfusion in neonates have often shown only weakly positive associations with blood pressure. OBJECTIVES: To examine the relationship between invasively monitored arterial blood pressure and four measurements of systemic perfusion: left and right ventricular outputs, superior vena caval (SVC) flow and descending aortic (DAo) flow. DESIGN: Echocardiographic assessments of perfusion were performed four times in the first 48 h of postnatal life in a cohort of 34 preterm (<30 weeks) infants. Arterial blood pressure was monitored invasively over the exact duration of the echocardiogram. RESULTS: In the first 48 h of postnatal life there was no evidence of a positive association between blood pressure and volume of blood flow in any of the four vessels studied. At 5 h postnatal age there was a weak but significant inverse correlation between volume of SVC flow and arterial blood pressure (p = 0.04). A similar but non-significant trend was seen at 12 h postnatal age. CONCLUSIONS: Infants with reduced systemic perfusion tend to have normal or high blood pressure in the first hours of life, suggesting that a high systemic vascular resistance may lead to reduced blood flow. Low blood pressure does not correlate with poor perfusion in the first 48 h of postnatal life in sick preterm infants.

Comparison of shuttle walk with measured peak oxygen consumption in patients with operable lung cancer.

BACKGROUND: The relationship between the shuttle walk test and peak oxygen consumption in patients with lung cancer has not previously been reported. A study was undertaken to examine this relationship in patients referred for lung cancer surgery to test the hypothesis that the shuttle walk test would be useful in this clinical setting. METHODS: 125 consecutive patients with potentially operable lung cancer were prospectively recruited. Each performed same day shuttle walking and treadmill walking tests. RESULTS: Shuttle walk distances ranged from 104 m to 1020 m and peak oxygen consumption ranged from 9 to 35 ml/kg/min. The shuttle walk distance significantly correlated with peak oxygen consumption (r = 0.67, p<0.001). All 55 patients who achieved more than 400 m on the shuttle test had a peak oxygen consumption of at least 15 ml/kg/min. Seventy of 125 patients failed to achieve 400 m on the shuttle walk test; in 22 of these the peak oxygen consumption was less than 15 ml/kg/min. Nine of 17 patients who achieved less than 250 m had a peak oxygen consumption of more than 15 ml/kg/min. CONCLUSION: The shuttle walk is a useful exercise test to assess potentially operable lung cancer patients with borderline lung function. However, it tends to underestimate exercise capacity at the lower range compared with peak oxygen consumption. Our data suggest that patients achieving 400 m on the shuttle walk test do not require formal measurement of oxygen consumption. In patients failing to achieve this distance we recommend assessment of peak oxygen consumption, particularly in those unable to walk 250 m, because a considerable proportion would still qualify for surgery as they had an acceptable peak oxygen consumption.

16-Detector multislice CT in the detection of stress fractures: a comparison with skeletal scintigraphy.

AIMS: To test the hypothesis that the improved resolution afforded by 16-detector computed tomography (CT) would translate to better stress fracture detection when compared with skeletal scintigraphy. MATERIALS AND METHODS: Thirty-three cases of suspected stress fractures in 26 patients were investigated using skeletal scintigraphy and 16-detector CT performed on the same day. Planar images of the lower limbs were taken 3h post-injection of 400MBq (99m)Tc-methylene diphosphonate ((99m)Tc-MDP). (99m)Tc-MDP uptake was quantified at suspected fracture sites. CT was performed using a 16-detector multisection machine employing 0.75mm detectors and images reconstructed in 0.5mm increments. Examinations were reported independently and discordant results were compared at follow-up. RESULTS: At initial reporting scintigraphy identified fractures in 13 of the 33 cases and CT identified four of the 33. In one case, on review of the CT images, a fracture was present in the distal fibula that was not initially identified. This resulted in eight scintigraphic-positive CT-negative discordant cases. The (99m)Tc-MDP uptake was significantly lower in the discordant fracture group compared with the concordant group (p<0.01). CONCLUSIONS: Despite technological advances in CT, scintigraphy appeared to detect more stress fractures. As such, multidetector CT should not be used as a routine initial investigation in stress fracture detection. The potential use of (99m)Tc-MDP quantification at fracture sites is of interest and may be worth further investigation.

16 detector multislice CT versus skeletal scintigraphy in the diagnosis of wrist fractures: value of quantification of 99Tcm-MDP uptake.

To compare the measured uptake of 99Tcm-methylene diphosphonate (99Tcm-MDP) in those scaphoid fractures seen on both 16 detector multislice CT and scintigraphy, with those seen only on scintigraphy. Over a 12 month period a total of 51 patients with suspected fracture underwent both conventional 99Tcm-MDP scintigraphy and 16 detector multislice CT on the same day. The 99Tcm-MDP uptake was then quantified in patients with identified fracture. This was measured by placing a region of interest (ROI) over the fracture site and the mean and maximum number of counts were compared with those in a similar size ROI placed over background bone activity. A total of 23 fractures were identified on scintigraphy of which 16 were also detected on CT (concordant). In seven cases the fracture was not seen on CT, even in retrospect (discordant). In the discordant cases, follow-up radiographs and MRI (where available) also failed to demonstrate a fracture. The mean fracture count to background bone activity ratio averaged 7.7 (range 3.2-18.5) for concordant fractures and 3.8 (range 1.7-5.3) for discordant fractures (t-test p=0.04). The maximum fracture count to background bone activity ratio averaged 12.7 (range 4.3-27.7) for concordant fractures and 6.3 (range 2.6-9.5) for discordant fractures (t-test p=0.03). It is speculated whether these discordant fractures with less 99Tcm-MDP uptake may represent a less severe injury such as bone bruise.

Relationship between pulmonary function and lung cancer surgical outcome.

The British Thoracic Society and American College of Chest Physician guidelines outline criteria for investigating patients for lung cancer surgery. However, the guidelines are based on relatively old studies. Therefore, the relationship between pulmonary function test results and surgical outcome were studied prospectively in a large cohort of lung cancer patients. From January 2001 to December 2003, 110 patients underwent surgery for lung cancer. All underwent full lung function testing in order to predict post-operative lung function. The hospital mortality rate was 3% and major complication rate 22%. There was poor overall outcome in 13%. Mean pre-operative lung function values were: forced expiratory volume in one second (FEV1) 2.0 L (79.4% of the predicted value), and carbon monoxide diffusing capacity of the lung (D(L,CO)) 73.6% pred. The mean post-operative lung function values were: FEV1 1.4 L (55.6% pred), and D(L,CO) 51.3% pred. All lung function values were better predictors of poor surgical outcome when expressed as a percentage of the predicted value. Using a threshold of pre-operative FEV1 of 47% pred resulted in the most useful positive and negative predictive probabilities, 0.90 and 0.67, respectively. Lung function values expressed as a percentage of the predicted value are more useful predictors of post-operative outcome than absolute values. The threshold of predicted forced expiratory volume in one second for surgical intervention could be lower (45-50% pred) than is currently accepted without increased mortality.

The absent kidney in 99Tcm-MAG3 renogram: a dramatic reversible consequence of contrast nephrotoxicity superimposed on renal obstruction.

99Tcm-mercaptoacetyltriglycine (MAG3) renogram is a robust imaging technique used to delineate upper urinary tract obstruction. The changes observed on the renogram are often reversible on relief of obstruction. We present two cases illustrating the extreme consequence of contrast nephrotoxicity on pre-existing obstructed kidneys. In one case, this led to severe impairment of perfusion and uptake observed on 99Tcm-MAG3 renogram and in the second case virtual non-visualization of the obstructed kidney. Subsequent treatment of obstruction, led to dramatic improvement in renal function. It is important for clinicians, nuclear medicine physicians and radiologists to be aware of the potential of contrast nephrotoxicity in obstructed kidneys.