Three-Dimensional Echocardiographic Analysis of Left Ventricular Function during Hemodialysis

Background: The effects of hemodialysis (HD) on left ventricular (LV) function have been studied by various echocardiographic techniques (M-mode, 2D echocardiography). These studies are hampered by a low accuracy of measurements because of geometric assumptions regarding LV shape. Three-dimensional echocardiography (3DE) overcomes this limitation. Methods: We tested the feasibility of 3DE assessment of LV function during HD. Conventional biplane Simpson rule (BSR) and single plane area length method (SPM) for LV function analysis were used as a reference. Results: 12 HD patients were studied and in 10 (83%) a total of 80 3D datasets were acquired. In 3 patients, one dataset (4%) was of insufficient quality and excluded from analysis. Correlation between SPM, BSR and 3DE for calculation of end-diastolic (EDV, r = 0.89 and r = 0.92, respectively), end-systolic volume (ESV, r = 0.92 and r = 0.93, respectively) and for ejection fraction (EF, r = 0.90 and r = 0.88, respectively) was moderate. Limits-of-agreement results for EDV and ESV were poor with confidence intervals larger than 30 ml. Both 2DE methods underestimated end-diastolic and end-systolic volume, while overestimating ejection fraction. Conclusion: 3DE is feasible for image acquisition during HD, which opens the possibility for accurate and reproducible measurement of LV function during HD. This may improve the assessment of the acute effect of HD on LV performance, and guide therapeutic strategies aimed at preventing intradialytic hypotension

⁸⁹Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy:A Feasibility Study

Background: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. Methods: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. Results: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of −48% and −90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. Conclusions: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.</p

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Variation in neurosurgical management of traumatic brain injury

Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

3D Harmonic Echocardiography:

Three dimensional (3D) echocardiography has recently developed from an experimental technique in the ’90 towards an imaging modality for the daily clinical practice. This dissertation describes the considerations, implementation, validation and clinical application of a unique concept for harmonic 3D echocardiography. Part I firstly illustrates the advantages of harmonic imaging with a new transducer design tool, allowing the simulation of steered nonlinear acoustic beams. Then this dissertation introduces the fast rotating ultrasound (FRU-) transducer, which serves as a cost effective alternative for full- volume echocardiography with optimal harmonic capabilities. Measurement of the left ventricular (LV) volume has major diagnostic and prognostic importance. In the part II this basic application of the FRU-transducer is explored. Both a commercially available and self-developed quantification application are evaluated for LV volume measurement. Both quant! ification applications use advanced semi-automatic detection algorithms for endocardial border delineation. In addition, the efficiency of LV volume quantification is optimized by determining the minimal number of long-axis images required for accurate LV volume measurement. More advanced applications are investigated in part III. First, 3D echocardiography during hemodialysis is compared with two dimensional echocardiography. The study gives a good example of the flexible application of 3D echocardiography. Subsequently, the advantages of 3D contrast harmonic imaging are explored. Whether 3D echocardiog

High frequency attenuation measurements of lipid encapsulated contrast agents

A number of recent studies have indicated the potential of ultrasound contrast agent imaging at high ultrasound frequencies. However, the acoustic properties of microbubbles at frequencies above 10 MHz remain poorly understood at present. In this study we characterize the high frequency attenuation properties of (1) BR14, (2) BR14 that has been mechanically filtered (1 and 2 μm pore sizes) to exclude larger bubbles, and (3) the micron to submicron agent BG2423. A narrowband pulse-echo substitution method is employed with a series of four transducers covering the frequency range from 2 to 50 MHz. For BR14, attenuation decreases rapidly from 2 to 10 MHz and then more gradually from 10 to 50 MHz. For 2 μm filtration, the attenuation peaks between 10 and 15 MHz. For 1 μm filtration, attenuation continues to rise until 50 MHz. The agent BG2423 exhibits a diffuse attenuation peak in the range of 15–25 MHz and remains high until 50 MHz. These results demonstrate a strong influence of bubble size on high frequency attenuation curves, with bubble diameters of 1–2 μm and below having more pronounced acoustic activity at frequencies above 10 MHz

Feasibility of 3D harmonic contrast imaging

Improved endocardial border delineation with the application of contrast agents should allow for less complex and faster tracing algorithms for left ventricular volume analysis. We developed a fast rotating phased array transducer for 3D imaging of the heart with harmonic capabilities making it suitable for contrast imaging. In this study the feasibility of 3D harmonic contrast imaging is evaluated in vitro. A commercially available tissue mimicking flow phantom was used in combination with Sonovue. Backscatter power spectra from a tissue and contrast region of interest were calculated from recorded radio frequency data. The spectra and the extracted contrast to tissue ratio from these spectra were used to optimize the excitation frequency, the pulse length and the receive filter settings of the transducer. Frequencies ranging from 1.66 to 2.35 MHz and pulse lengths of 1.5, 2 and 2.5 cycles were explored. An increase of more than 15 dB in the contrast to tissue ratio was found around the second harmonic compared with the fundamental level at an optimal excitation frequency of 1.74 MHz and a pulse length of 2.5 cycles. Using the optimal settings for 3D harmonic contrast recordings volume measurements of a left ventricular shaped agar phantom were performed. Without contrast the extracted volume data resulted in a volume error of 1.5%, with contrast an accuracy of 3.8% was achieved. The results show the feasibility of accurate volume measurements from 3D harmonic contrast images. Further investigations will include the clinical evaluation of the presented technique for improved assessment of the heart