Routine Clinical Protocols Research Articles

Treatment of primary graft dysfunction after lung transplantation with orally inhaled AP301: A prospective, randomized pilot study

Primary graft dysfunction (PGD) after lung transplantation (LTx) carries significant morbidity and mortality in the early post-operative period and is associated with the development of chronic lung allograft dysfunction. AP301, an activator of epithelial sodium channel-mediated Na+ uptake represents a new concept for prevention and treatment of pulmonary edema and has shown promising results in the pre-clinical setting. This pilot study investigated the clinical effect of inhaled AP301 on patients with development of PGD > 1 according to International Society of Heart and Lung Transplantation criteria after primary LTx in a high-volume center and was conducted as a randomized, placebo-controlled, single-center pilot-study including 20 patients. All consecutive patients fulfilling inclusion criteria were screened for PGD at arrival on the intensive care unit (ICU) after LTx. After randomization, inhaled AP301 or placebo was administered by nebulizer twice daily for 7 days or until extubation. Otherwise, patients were treated according to routine clinical protocol. Partial pressure of arterial oxygen (Pao2)/fraction of inspired oxygen (Fio2) values were obtained until extubation and assessed as a primary outcome parameter. Patients were monitored for 30 days within the study protocol. From July 2013 to August 2014, 20 patients were randomized 1:1 to AP301 (Group 1) or placebo (Group 2). Both groups were comparable with regard to sex (40% women/60% men vs 50% women/50% men), mean age (55 ± 13 vs 54 ± 6 years), comorbidities, and diagnosis leading to LTx. The Pao2/Fio2 ratio at the time of inclusion was comparable in both groups, with a mean 235.65 ± 90.78 vs 214.2 ± 95.84 (p = 0.405), and there was no significant difference in the extravascular lung water index (13.88 ± 5.28 vs 16 ± 6.29 ml/kg, p = 0.476). The primary end point was mean Pao2/Fio2 ratio values between baseline and Day 3. In the AP301 group, only 1 patient was ventilated at Day 4 and no patients were ventilated after Day 4. In the placebo group, 5 patients were ventilated on Day 4 and 2 patients on Days 5, 6, and 7. The mean increase in the Pao2/Fio2 ratio was significantly higher in Group 1 patients, and the mean between baseline and at 72 hours was 365.6 ± 90.4 in Group 1 vs 335.2 ± 42.3 in Group 2 (p = 0.049). The duration of intubation was shorter in Group 1 than in Group 2 patients (2 ± 0.82 vs 3.7 ± 1.95 days; p = 0.02). ICU stay was 7.5 ± 3.13 days in Group 1 vs 10.8 ± 8.65 days in group 2 (p = 0.57). Survival at 30 days was 100%. No severe adverse events were recorded. This study was designed as a proof-of-concept pilot study. Although it was not powered to achieve statistical significances, the study demonstrated relevant clinical effects of inhaled AP301 on patients with PGD after primary LTx. The improved gas exchange led to a significantly shorter duration of mechanical ventilation and a trend towards a shorter ICU stay. Further investigation of AP301 for treatment of PGD in larger studies is warranted. The trial is registered at https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000716-21/AT.

Imaging adult patients with Fontan circulation

Survival after the Fontan procedure for palliation of single ventricle congenital heart disease has improved. However, adults with Fontan circulation are at risk for several complications including heart failure, thromboembolism, and protein-losing enteropathy. This review discusses the role of noninvasive imaging for surveillance and early detection of anatomic and functional abnormalities of the Fontan circulation that can impact the risk for Fontan failure over time. Echocardiography is the first-line imaging modality for the adult Fontan patient. Use of established techniques, such as tissue Doppler imaging, and newer techniques, such as myocardial deformation and three-dimensional imaging, has improved the ability of echocardiography to serially assess ventricular and valvular function in this population. Strain imaging, in particular, is effective for early detection of subclinical ventricular dysfunction, is reproducible and can be incorporated into a routine clinical echocardiography protocol. Cardiac magnetic resonance (CMR) imaging complements echocardiography and overcomes the limitation of poor acoustic windows in adult patients, especially with regards to visualizing the cavopulmonary anastomoses and pulmonary arteries. High resolution imaging with CMR provides reliable assessment of ventricular size and function. Novel techniques utilizing CMR, such as computational fluid dynamics, have provided important insights into Fontan fluid dynamics, and the impact of Fontan geometry on flow efficiency through the circulation. Recent advances in echocardiography and CMR have improved detection of structural and functional abnormalities in adults with Fontan circulation and are essential in monitoring for complications in this growing population.

Cochlear Implant Electrode Localization Using an Ultra-High Resolution Scan Mode on Conventional 64-Slice and New Generation 192-Slice Multi-Detector Computed Tomography.

A new generation 192-slice multi-detector computed tomography (MDCT) clinical scanner provides enhanced image quality and superior electrode localization over conventional MDCT. Currently, accurate and reliable cochlear implant electrode localization using conventional MDCT scanners remains elusive. Eight fresh-frozen cadaveric temporal bones were implanted with full-length cochlear implant electrodes. Specimens were subsequently scanned with conventional 64-slice and new generation 192-slice MDCT scanners utilizing ultra-high resolution modes. Additionally, all specimens were scanned with micro-CT to provide a reference criterion for electrode position. Images were reconstructed according to routine temporal bone clinical protocols. Three neuroradiologists, blinded to scanner type, reviewed images independently to assess resolution of individual electrodes, scalar localization, and severity of image artifact. Serving as the reference standard, micro-CT identified scalar crossover in one specimen; imaging of all remaining cochleae demonstrated complete scala tympani insertions. The 192-slice MDCT scanner exhibited improved resolution of individual electrodes (p < 0.01), superior scalar localization (p < 0.01), and reduced blooming artifact (p < 0.05), compared with conventional 64-slice MDCT. There was no significant difference between platforms when comparing streak or ring artifact. The new generation 192-slice MDCT scanner offers several notable advantages for cochlear implant imaging compared with conventional MDCT. This technology provides important feedback regarding electrode position and course, which may help in future optimization of surgical technique and electrode design.

Prediction of graft-versus-host disease: a biomarker panel based on lymphocytes and cytokines.

Graft-versus-host disease (GvHD) still belongs to the major challenges after allogeneic hematopoietic stem cell transplantation (HSCT). Immune-suppressive therapy against GvHD is a double-edged sword due to risk of infections and relapse. The ability to adapt prophylactic treatment according to the probability of severe GvHD would be an essential advantage for the patients. We analyzed different biomarkers for their potential to predict the development of GvHD in 28 patients who underwent allogeneic HSCT. Blood was taken once directly after hematopoietic engraftment. In this study, patients were monitored for 12months after HSCT for the occurrence of acute GvHD or acute/chronic GvHD overlap syndrome. Soluble IL-2 receptor and CD4/CD8 T cell ratio were independently associated with the occurrence of GvHD in the observation period. However, the largest area under the receiver operating characteristic curve with 0.90 was observed when a 5-parameter biomarker score based on CD4+ T cells, CD8+ T cells, CD19- CD21+ precursor B cells, CD4/CD8 T cell ratio, and soluble IL-2 receptor was used to predict GvHD. In addition, CD8+ T cell levels above 2.3% of all mononuclear cells after engraftment may predict relapse-free survival at least for 12months. In summary, we found a new biomarker panel for prediction of GvHD which is featured by established laboratory assays and high statistical significance. In order to introduce the biomarker panel into routine clinical protocols, we suggest performing a larger multi-center study.

Image noise and dose performance across a clinical population: Patient size adaptation as a metric of CT performance.

Modern CT systems adjust X-ray flux accommodating for patient size to achieve certain image noise values. The effectiveness of this adaptation is an important aspect of CT performance and should ideally be characterized in the context of real patient cases. The objective of this study was to characterize CT performance with a new metric that includes image noise and radiation dose across a clinical patient population. The study included 1526 examinations performed by three CT scanners (one GE Healthcare Discovery CT750HD, one GE Healthcare Lightspeed VCT, and one Siemens SOMATOM definition Flash) used for two routine clinical protocols (abdominopelvic with contrast and chest without contrast). An institutional monitoring system recorded all the data involved in the study. The dose-patient size and noise-patient size dependencies were linearized by considering a first-order approximation of analytical models that describe the relationship between ionization dose and patient size, as well as image noise and patient size. A 3D-fit was performed for each protocol and each scanner with a planar function, and the root mean square error (RMSE) values were estimated as a metric of CT adaptability across the patient population. The data show different scanner dependencies in terms of adaptability: the RMSE values for the three scanners are between 0.0385 HU1/2 and 0.0215 HU1/2 . A theoretical relationship between image noise, CTDIvol , and patient size was determined based on real patient data. This relationship may be interpreted as a new metric related to the scanners' adaptability concerning image quality and radiation dose across a patient population. This method could be implemented to investigate the adaptability related to other image quality indexes and radiation dose in a clinical population.

Usefulness of an injectable anaesthetic protocol for semen collection through urethral catheterisation in domestic cats.

Objectives Although less often requested in comparison with dogs, the collection of semen in cats can be necessary for artificial insemination, for semen evaluation in tom cats used for breeding and for semen storage. Urethral catheterisation after pharmacological induction with medetomidine has proved to be useful for the collection of semen in domestic cats. However, most of the previously used protocols require the administration of high doses of medetomidine that can increase the risk of side effects, especially on the cardiovascular system. In routine clinical practice, one safe and useful injectable anaesthetic protocol for short-term clinical investigations or surgery in cats involves premedication with low intramuscular doses of dexmedetomidine with methadone, followed by intravenous propofol bolus injection. We aimed to assess the usefulness of this injectable anaesthetic protocol for semen collection, via urethral catheterisation, in domestic cats. Methods The study was performed on 38 purebred, adult cats, during the breeding season, and semen was collected via urethral catheterisation using an injectable anaesthesia protocol with methadone (0.2 mg/kg) and dexmedetomidine (5 µg/kg) premedication, followed by induction with propofol. Results The anaesthetic protocol used in the present study allowed the collection of large-volume semen samples, characterised by good parameters and without side effects. Conclusions and relevance The results from the present study suggest that the injectable anaesthetic protocol using methadone and dexmedetomidine premedication, followed by induction with propofol, could be suitable and safe for the collection of a good-quality semen sample, via urethral catheterisation, in domestic cats. It can therefore be used as an alternative to previous medetomidine-based sedation protocols.

T2-Imaging Changes in the Nigrosome-1 Relate to Clinical Measures of Parkinson's Disease.

The nigrosome-1 region of the substantia nigra (SN) undergoes the greatest and earliest dopaminergic neuron loss in Parkinson's disease (PD). As T2-weighted magnetic resonance imaging (MRI) scans are often collected with routine clinical MRI protocols, this investigation aims to determine whether T2-imaging changes in the nigrosome-1 are related to clinical measures of PD and to assess their potential as a more clinically accessible biomarker for PD. Voxel intensity ratios were calculated for T2-weighted MRI scans from 47 subjects from the Parkinson's Progression Markers Initiative database. Three approaches were used to delineate the SN and nigrosome-1: (1) manual segmentation, (2) automated segmentation, and (3) area voxel-based morphometry. Voxel intensity ratios were calculated from voxel intensity values taken from the nigrosome-1 and two areas of the remaining SN. Linear regression analyses were conducted relating voxel intensity ratios with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sub-scores for each subject. For manual segmentation, linear regression tests consistently identified the voxel intensity ratio derived from the dorsolateral SN and nigrosome-1 (IR2) as predictive of nBehav (p = 0.0377) and nExp (p = 0.03856). For automated segmentation, linear regression tests identified IR2 as predictive of Subscore IA (nBehav) (p = 0.01134), Subscore IB (nExp) (p = 0.00336), Score II (mExp) (p = 0.02125), and Score III (mSign) (p = 0.008139). For the voxel-based morphometric approach, univariate simple linear regression analysis identified IR2 as yielding significant results for nBehav (p = 0.003102), mExp (p = 0.0172), and mSign (p = 0.00393). Neuroimaging biomarkers may be used as a proxy of changes in the nigrosome-1, measured by MDS-UPDRS scores as an indicator of the severity of PD. The voxel intensity ratio derived from the dorsolateral SN and nigrosome-1 was consistently predictive of non-motor complex behaviors in all three analyses and predictive of non-motor experiences of daily living, motor experiences of daily living, and motor signs of PD in two of the three analyses. These results suggest that T2 changes in the nigrosome-1 may relate to certain clinical measures of PD. T2 changes in the nigrosome-1 may be considered when developing a more accessible clinical diagnostic tool for patients with suspected PD.

Accuracy of SWI sequences compared to T2*-weighted gradient echo sequences in the detection of cerebral cavernous malformations in the familial form.

The purpose of this study was to assess the accuracy of susceptibility-weighted imaging (SWI), compared with T2*-weighted gradient echo (GRE) imaging in assessing cerebral cavernous malformations. We retrospectively evaluated 21 patients with a familial form of cavernous malformation. Magnetic resonance (MR) protocol included non-enhanced and contrast-enhanced fast-spin echo (FSE) T1-weighted sequences, FSE T2-weighted sequences, fluid-attenuated inversion-recovery (FLAIR), GRE T2*-weighted and SWI sequences. Images were reviewed in consensus by two expert neuroradiologists to assess the location, number, size and conspicuity of the lesions on T2*-weighted GRE and SWI sequences. Statistical differences in the number, size and conspicuity of the lesions seen on the SWI images and the T2*-weighted GRE images were assessed with the nonparametric Wilcoxon signed rank test. The number of cavernous malformations was significantly higher (p < .001) on the SWI images (n = 152) than on T2*-weighted GRE images (n = 56). Lesion size was significantly higher (p < .001) on SWI images (mean: 0.4 cm, SD ± 0.55) than on T2*-weighted GRE sequences (mean: 0.2 cm, SD ± 0.51) and the differences were statistically significant (p < .001). Lesion conspicuity was significant higher (p < .001) on SWI than on T2*-weighted GRE images. In one patient who underwent a 2-month follow-up for the onset of neurologic symptoms related to cerebral hemorrhage, a cerebral hematoma was identified at the site of a cerebral cavernous malformation that was demonstrated only on the SWI images in the previous MR examination. The SWI sequence, being more sensitive to substances which distort the local magnetic field than the GRE T2*W sequence, showed a higher sensitivity in identifying cerebral cavernous malformations. Thus, routine clinical neuroimaging protocol should contain SWI sequences to evaluate patients with (or suspected) cerebral cavernous malformations.

Correcting motion in multiplanar cardiac magnetic resonance images.

BackgroundMisalignment in cardiac magnetic resonance (CMR) images can adversely affect three-dimensional left ventricle modelling and downstream quantitative analysis. Currently, there are two types of approaches for dealing with realignment and motion distortion problems, one image based and the other geometry based. Image-based approaches are limited by the inherent non-homogeneity and anisotropy of CMR images. Geometry-based approaches rely on idealized models and over-simplified assumptions. This study was motivated by the need for a robust and effective approach for correcting motion related distortions due to misalignment in CMR images.MethodsA cine cardiac magnetic resonance image sequence was acquired using our routine clinical imaging protocol. The left ventricular endocardium was delineated manually with software assistance on all long and short-axis images. Long and short-axis contours were projected onto a patient-based coordinate system and then realigned using iterative registration. The realigned contour points were used to reconstruct the shape of the left ventricle for quantitative validation.ResultsThe method was tested on five myocardial infarction patients whose images showed substantial misalignment. Realignment time was about 16 seconds per case, using a 2.5 GHz CPU desktop with obvious elimination of the distortion in the reconstructed model. Using the long-axis contour as a reference in evaluating the reconstructed models, it was apparent that the models with realigned contours had better accuracy than the non-realigned ones.ConclusionThis study presents a novel, geometry-based method for correcting motion distortions in CMR images. The method incorporates (1) manual delineation, (2) registration based on a generalized, iterative closest point algorithm, and (3) reconstruction of the shape of the left ventricle for quantitative validation. The effectiveness of our approach is corroborated both visually and by quantitative assessment. We envision the use of our method in current clinical practice as a means of improving accuracy in the evaluation of cardiac function.

Achieving Consensus in the Measurement of Psychological Adjustment to Cleft Lip and/or Palate.

Psychological adjustment to cleft lip/palate is multifaceted and can fluctuate over time and across different situations. Consequently, a comprehensive understanding of adjustment is difficult to capture, and the challenge of achieving consensus among researchers and clinicians regarding key constructs and processes is considerable. Numerous measures have been used in research and clinical audit, resulting in conflicting findings and difficulties in evidencing the value of psychological intervention. The launch of the world's largest cleft lip/palate cohort study has provided an opportunity to standardize data collection across the United Kingdom. To describe the collaborative process used to achieve consensus in the academic and clinical measurement of psychological adjustment to cleft lip/palate. Extensive work based on existing literature and clinical experience has resulted in a conceptual framework comprising six domains of adjustment and corresponding risk/protective factors that are measureable across key developmental time points. Driven by this framework, a core pack of standardized measures has been selected according to psychometric properties, clinical utility, and pragmatic considerations. To date, these measures have been implemented within a UK-wide longitudinal cohort study (at diagnosis, 18 months, 3 years, 5 years, and 8 years) and adopted into the national routine clinical audit protocol for cleft lip/palate at age 5. Further data collection points will follow as the cohorts age. Over time, consistency in data collection will allow researchers to address some of the key unanswered questions in relation to psychological adjustment to cleft lip/palate.

Evaluation of Focal Cervical Spinal Cord Lesions in Multiple Sclerosis: Comparison of White Matter-Suppressed T1 Inversion Recovery Sequence versus Conventional STIR and Proton Density-Weighted Turbo Spin-Echo Sequences.

Conventional MR imaging of the cervical spinal cord in MS is challenged by numerous artifacts and interreader variability in lesion counts. This study compares the relatively novel WM-suppressed T1 inversion recovery sequence with STIR and proton density-weighted TSE sequences in the evaluation of cervical cord lesions in patients with MS. Retrospective blinded analysis of cervical cord MR imaging examinations of 50 patients with MS was performed by 2 neuroradiologists. In each patient, the number of focal lesions and overall lesion conspicuity were measured in the STIR/proton density-weighted TSE and WM-suppressed T1 inversion recovery sequence groups. Independent side-by-side comparison was performed to categorize the discrepant lesions as either "definite" or "spurious." Lesion contrast ratio and edge sharpness were independently calculated in each sequence. Substantial interreader agreement was noted on the WM-suppressed T1 inversion recovery sequence (κ = 0.82) compared with STIR/proton density-weighted TSE (κ = 0.52). Average lesion conspicuity was better on the WM-suppressed T1 inversion recovery sequence (conspicuity of 3.1/5.0 versus 3.7/5.0, P < .01, in the WM-suppressed T1 inversion recovery sequence versus STIR/proton density-weighted TSE, respectively). Spurious lesions were more common on STIR/proton density-weighted TSE than on the WM-suppressed T1 inversion recovery sequence (23 and 30 versus 3 and 4 by readers 1 and 2, respectively; P < .01). More "definite" lesions were missed on STIR/proton density-weighted TSE compared with the WM-suppressed T1 inversion recovery sequence (37 and 38 versus 3 and 6 by readers 1 and 2, respectively). Lesion contrast ratio and edge sharpness were highest on the WM-suppressed T1 inversion recovery sequence. There is better interreader consistency in the lesion count on the WM-suppressed T1 inversion recovery sequence compared with STIR/proton density-weighted TSE sequences. The focal cord lesions are visualized with better conspicuity due to better contrast ratio and edge sharpness. There are fewer spurious lesions on the WM-suppressed T1 inversion recovery sequence compared with STIR/proton density-weighted TSE. The WM-suppressed T1 inversion recovery sequence could potentially be substituted for either STIR or proton density-weighted TSE sequences in routine clinical protocols.

Single nucleotide polymorphisms and risk factors predictive of pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease progressing asymptomatically until death within months after diagnosis. Defining at-risk populations should promote an early diagnosis and efficient follow-up, therefore avoiding its development. Single nucleotide polymorphisms, or SNPs, constitute the most abundant form of genetic variation in the human genome. SNPs are markers of diverse populations or individuals, yet also can be associated with differences in susceptibility or severity of certain diseases and/or individual responses to drugs. Many SNPs have previously been identified in studies of healthy subjects and patients with different alleles of a given gene. To date, around forty SNPs from the human genome have been correlated with predisposition to PDAC by pan-genomic studies or genome wide association studies (GWAS). However, parts of the human genome located within the GC-rich repeated domain of chromosomes are unsuitable for GWAS. Unfortunately, of those forty SNPs none are currently used in routine clinical protocols as potential biomarkers for PDAC. Exon 11 of the bile salt-dependent lipase gene ( BSDL ) plays a key role in pancreatic disease and encodes variable number of tandem repeat (VNTR) sequences, therefore Martinez et al . [Oncotarget. 2015; 6: 39855-39864.] hypothesized that a genetic link exists between mutations in VNTR loci and predisposition to pancreatic cancer (PC). Authors reported that the c.1719C>T transition (SNP rs488087) present in BSDL VNTR may be a useful marker for defining a population at risk of developing PC (occurrence: 63.90% in the PC group versus 27.30% in the control group). Notably, the odds ratio (OR) of 4.7 for the T allele was larger than those already determined for other SNPs suspected to be predictive of PC. Further studies on tumor pancreatic tissue suggested that the T allele may favor Kras G12R/G12D somatic mutations which represent negative prognostic factors associated with reduced survival. Furthermore, a robust method using probes for droplet digital (dd)-PCR was designed to specifically discriminate the C/C major from C/T or T/T minor genotypes. Altogether, Martinez et al . propose that detection of the T allele in rs488087 SNP should lead to an in-depth follow-up of these patients, particularly if associated with other potential risk factors of PC.

Measurement of arteriolar blood volume in brain tumors using MRI without exogenous contrast agent administration at 7T.

Arteriolar cerebral-blood-volume (CBVa) is an important perfusion parameter that can be measured using inflow-based vascular-space-occupancy (iVASO) MRI without exogenous contrast agent administration. The purpose of this study is to assess the potential diagnostic value of CBVa in brain tumor patients by comparing it with total-CBV (including arterial, capillary and venous vessels) measured by dynamic-susceptibility-contrast (DSC) MRI. Twelve brain tumor patients were scanned using iVASO (on 7T as part of a research project) and DSC (on 3T as part of routine clinical protocols) MRI. Region-of-interest analysis was performed to compare the resulting perfusion measures between tumoral and contralateral regions, and to evaluate their associations with tumor grades. CBVa measured by iVASO MRI significantly correlated with WHO grade (ρ = 0.37, P = 0.04). Total-CBV measured by DSC MRI showed a trend of correlation with WHO grade (ρ = 0.28, P = 0.5). The signal-to-noise ratio was comparable (P > 0.1) between the two methods, while the contrast-to-noise ratio between tumoral and contralateral regions was higher in iVASO-CBVa than DSC-CBV in WHO II/III patients (P < 0.05) but comparable in WHO IV patients (P > 0.1). A trend of positive correlation between DSC-CBV and iVASO-CBVa was observed (R2 = 0.28, P = 0.07). In this initial patient study, CBVa demonstrated a stronger correlation with WHO grade than total-CBV. Further investigation with a larger cohort is warranted to validate whether CBVa can be a better classifier than total-CBV for the stratification of brain tumors, and whether iVASO MRI can be a useful alternative method for the assessment of tumor perfusion, especially when exogenous contrast agent administration is difficult in certain patient populations. J. Magn. Reson. Imaging 2016;44:1244-1255.

COMPUTED TOMOGRAPHY DOSE INDEX MEASUREMENT FOR Hi-ART MEGAVOLTAGE HELICAL CT.

On-line megavoltage computed tomography (MVCT) images are used to verify patient daily set-up in Hi-ART helical TomoTherapy unit. To evaluate the patient dose from MVCT scanning in image guidance, weighted computed tomography (CT) dose index (CTDIw) was measured with PTW TM30009 CT pencil chamber in head and body phantoms for slice thicknesses of 2, 4 and 6 mm with different scan lengths. Dose length products (DLPs) were subsequently calculated. The CTDIw and DLP were compared with XVI kV CBCT and Brilliance simulator CT for routine clinical protocols. It was shown that CTDI and DLP had close relationship with the slice thickness and the scan length. The dose distribution in the transversal plane was very inhomogeneous due to the attenuation of the couch. Patient dose from MVCT was lower than XVI CBCT for the head scan, while larger for body scan. CTDIw, which is measured easily and reproducibly, can be used to assess the patient dose in MVCT. Regular measurement should be performed in QA & QC programmes. Appropriate slice thickness and scan range should be chosen to reduce the patient dose.

Feasibility study of low tube voltage (80 kVp) coronary CT angiography combined with contrast medium reduction using iterative model reconstruction (IMR) on standard BMI patients.

To investigate the feasibility of low-tube-voltage (80 kVp) coronary CT angiography (CCTA) combined with contrast medium (CM) reduction and iterative model reconstruction (IMR) on patients with standard body mass index compared with clinical routine protocol. Retrospectively gated helical CCTA scans were acquired using a 256-slice multi-slice CT (Brilliance iCT; Philips Healthcare, Cleveland, OH) on 94 patients with standard body mass index (20-25 kg m(-2)) who were randomly assigned into 2 groups. The scan protocol for Group 1 was 100 kVp and 600 mAs with 70 ml CM at an injection rate of 4.5-5.5 ml s(-1); images were reconstructed by a hybrid iterative reconstruction technique (iDose(4); Philips Healthcare). Group 2 was scanned at 80 kVp and 600 mAs with 35 ml CM at an injection rate of 3.5-4.5 ml s(-1); images were reconstructed with IMR. Objective measurements such as the mean image noise and contrast-to-noise ratio of the two groups were measured on CT images and compared using the paired t-test. In addition, a subjective image quality evaluation was performed by two radiologists who were blinded to the scan protocol, using a 5-point scale [1 (poor) to 5 (excellent)]. The results of the two groups were compared using Mann-Whitney U test. The iodine delivery rate of Group 2 was 1.0 ± 0.5 gI s(-1) compared with 2.1 ± 0.5 gI s(-1) in Group 1 resulting in a reduction of 52.4%. In addition, an effective radiation dose reduction of 56.4% was achieved in Group 2 (2.4 ± 1.2 mSv) compared with Group 1 (5.5 ± 1.4 mSv). The mean CT attenuation, contrast-to-noise ratio and image quality of all segments in Group 2 were significantly improved compared with those in Group 1 (all, p < 0.01). The use of IMR along with a low tube voltage (80 kVp) combined with a low CM protocol for CCTA can reduce both radiation and CM dose with improved image quality. In this study, we used a novel knowledge-based IMR which remarkably reduced the image noise. We compared the quality of the images obtained when the tube voltage was reduced to 80 kVp and that of those obtained according to the clinical routine protocols to determine whether ultra-low-dose imaging plus IMR is feasible in CCTA scans. We found that a low dose protocol combined with 80 kVp and reduced CM for CCTA can reduce both radiation dose and CM dose with improved image quality by the use of IMR in non-obese patients.

Variation of patient imaging doses with scanning parameters for linac-integrated kilovoltage cone beam CT.

To evaluate the Elekta kilovoltage CBCT doses and the associated technical protocols with patient dosimetry estimation. Image guidance technique with cone-beam CT (CBCT) in radiation oncology on a daily basis can deliver a significant dose to the patient. To evaluate the patient dose from LINAC-integrated kV cone beam CT imaging in image-guided radiotherapy. CT dose index (CTDI) were measured with PTW TM30009 CT ion chamber in air, in head phantom and body phantom, respectively; with different combinations of tube voltage, current, exposure time per frame, collimator and gantry rotation range. Dose length products (DLP) were subsequently calculated to account for volume integration effects. The CTDI and DLP were also compared to AcQSim™simulator CT for routine clinical protocols. Both CTDIair and CTDIw depended quadratically on the voltage, while linearly on milliampere x seconds (mAs) settings. It was shown that CTDIw and DLP had very close relationship with the collimator settings and the gantry rotation ranges. Normalized CTDIw for Elekta XVI™CBCT was lower than that of ACQSim simulator CT owing to its pulsed radiation output characteristics. CTDIw can be used to assess the patient dose in CBCT due to its simplicity for measurement and reproducibility. Regular measurement should be performed in QA & QC program. Optimal image parameters should be chosen to reduce patient dose during CBCT.

Low-Volume Contrast Medium Protocol for Comprehensive Cardiac and Aortoiliac CT Assessment in the Context of Transcatheter Aortic Valve Replacement

To investigate the diagnostic performance of a comprehensive computed tomography (CT) protocol for both cardiac and aortoiliac evaluation of patients considered for transcatheter aortic valve replacement (TAVR) using a single, low-volume contrast medium (CM) injection. Forty-four TAVR candidates were retrospectively analyzed. All underwent retrospectively electrocardiogram-gated cardiac CT followed by high-pitch CT angiography of the aortoiliac vasculature using one of two single injection protocols of 320 mgI/mL iodine CM: group A (n = 22), iodine delivery rate-based (1.28 gI/s), 60-mL CM volume, 4.0 mL/s flow rate; group B (n = 22), clinical routine protocol, 100-mL CM volume, 4.0 mL/s flow rate. Mean arterial attenuation, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were calculated. Subjective image quality was assessed. Aortic root and iliofemoral dimensions could be analyzed in all cases. Patient characteristics showed no significant differences. Mean attenuation at the levels of the aortic root (285.8 ± 83.0 HU vs 327.5 ± 70.8 HU, P = .080) and the iliofemoral access route (256.8 ± 88.5 HU vs 307.5 ± 93.2 HU, P = .071), as well as SNR and CNR were nonsignificantly lower in group A compared to group B. Subjective image quality was equivalent. In multimorbid TAVR patients, the performance of a combined CT protocol using a single low-volume CM bolus is feasible with maintained image quality compared to a standard protocol.

Coronary calcium scores are systematically underestimated at a large chest size: A multivendor phantom study

ObjectiveTo evaluate the effect of chest size on coronary calcium score (CCS) as assessed with new-generation CT systems from 4 major vendors. MethodsAn anthropomorphic, small-sized (300 × 200 mm) chest phantom containing 100 small calcifications (diameters, 0.5–2.0 mm) was evaluated with and without an extension ring on state-of-the-art CT systems from 4 vendors. The extension ring was used to mimic a patient with a large chest size (400 × 300 mm). Image acquisition was repeated 5 times with small translations and/or rotations. Routine clinical acquisition and reconstruction protocols for small and large patients were used. CCS was quantified as Agatston and mass scores with vendor software. ResultsThe small-sized phantom resulted in median (interquartiles) Agatston scores of 10 (9–35), 136 (123–146), 34 (30–37), and 87 (85–89) for Philips, GE, Siemens, and Toshiba, respectively. Mass scores were 4 mg (3–9 mg), 23 mg (21–27 mg), 8 mg (8–9 mg), and 20 mg (20–20 mg), respectively. Adding the extension ring resulted in reduced Agatston scores for all vendors (17%–48%) and mass scores for 2 vendors (11%–49%). Median Agatston scores decreased to 9 (5–10), 79 (60–80), 27 (24–32), and 45 (29–53) units, and median mass scores remained similar for Philips at 4 mg (4–6 mg) and Siemens at 8 mg (7–8 mg) and decreased for the other vendors to 13 mg (11–14 mg) and 10 mg (8–13 mg), respectively. ConclusionThis multivendor phantom study showed that CCS can be underestimated up to 50% (49%–66%) for Agatston scores and 49% (36%–59%) for mass scores at a larger chest size, which may be relevant for women and large patients. However, CCS underestimation by chest size differs considerably by vendor.

Native T1 myocardial tissue characterisation in patients with pulmonary hypertension: findings from International T1 Multicentre Study

Background Pulmonary hypertension is a severe disorder characterized by elevated pulmonary artery pressure leading to right ventricular (RV) failure and premature death. We have recently shown that high signal in septal myocardium by cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) imaging indicates more severe disease. This study investigated whether markers of interstitial septal changes by T1 mapping relate to parameters of biventricular function and structure and makers of disease severity in pulmonary hypertension. Methods Patients with a suspected or established diagnosis of pulmonary hypertension, based on a previous echocardiography or catheterisation, respectively, and control subjects underwent routine clinical CMR protocol (1.5 and 3 Tesla) and T1 mapping prior to and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. T1 values were measured in mid-ventricular slices conservatively within septal myocardium. To transform native T1 values into a binary variable (normal/abnormal), the established cut-offs of >990ms at 1.5T or >1090ms at 3T, respectively, were used. For comparison of two and more than two normally distributed variables, Student’s t-test and one-way analysis of variance (ANOVA, with Bonferroni’s post-hoc test) as appropriate. Associations were explored by single and multivariate linear regressions. Results

Native T1 in Discrimination of Acute and Convalescent Stages in Patients With Clinical Diagnosis of Myocarditis: A Proposed Diagnostic Algorithm Using CMR

ObjectivesThis study investigated whether T1 mapping by cardiac magnetic resonance (CMR) reflects the clinical evolution of disease in myocarditis and supports its diagnosis independently of the disease stages. BackgroundAcute viral myocarditis is characterized by a range of intracellular changes due to viral replication and extracellular spill of debris within days of viral infection. Convalescence may be characterized by a chronic low-grade inflammation leading to ventricular remodelling, but also a complete resolution of myocardial changes. MethodsPatients with clinical diagnosis of viral myocarditis (N = 165) underwent routine clinical CMR protocol (1.5- and 3.0-T) for assessment of cardiac function and structure, and tissue characterization with T2-weighted imaging and late gadolinium enhancement. T1 mapping was obtained in a mid-ventricular short-axis slice before and >20 min after administration of 0.2 mmol/kg of gadobutrol. ResultsCompared with control subjects (n = 40), T1 indexes were increased in patients with myocarditis. Patients with acute symptoms (n = 61) had higher values of T1 indexes compared with patients in clinical convalescence (n = 67). Native T1 is an independent discriminator between health and disease, as well as a discriminator between acute and convalescent stage of the disease. Native T1- was superior to T2-weighted imaging and late gadolinium enhancement with high diagnostic accuracy and positive and negative predictive values. Using pre-defined cutoff values for normal ranges, we demonstrated that acute myocarditis can be independently identified by native T1 of >5 SD above the mean of normal range, whereas convalescence is best defined by either abnormal native T1 (>2 SD) or presence of late gadolinium enhancement. We prospectively tested a new diagnostic algorithm in an independent dataset of patients with clinical diagnosis of myocarditis and achieved similar diagnostic performance. ConclusionsThe new diagnostic algorithm using native T1 can reliably discriminate between health and disease and determine the clinical disease stage in patients with a clinical diagnosis of myocarditis.