High-end MRI scanner adapts automatically to individual anatomical and physiological characteristics

Magnetom Vida, the new high-end 3-Tesla MRI scanner with BioMatrix
technology from Siemens Healthineers, was launched to the public at University Hospital Tübingen, where the first system is installed. It has been undergoing clinical tests in the hospital’s Department for Diagnostic and Interventional Radiology since December 2016.

Magnetom Vida is the first scanner equipped with BioMatrix, a brand-new, innovative scanner technology that addresses inherent anatomical and physiological differences among individual patients, as well as variability among users. Magnetom Vida and BioMatrix allow users to meet the growing demand for MR imaging, perform the full range of routine as well as complex examinations, and deliver robust results for every patient. Furthermore, the scanner also makes MRI more cost-effective by reducing rescans and increasing productivity. High-precision imaging means that radiologists can deliver essential and robust information to choose the right treatment for each patient every time. Siemens Healthineers, in collaboration with its customers, is playing an important role in taking healthcare forward in the development of precision medicine.

Siemens Healthineers has been developing this disruptive and innovative BioMatrix technology for over five years. Its introduction represents a further advance in MRI imaging as well as the next level of automation and patient centricity.

High image quality and efficient workflows – regardless of user or patient
Due to high levels of exam variability, MRI is often considered to be one of the most complex medical imaging modalities. Physiological and anatomical differences between patients as well as different experiences levels in users contribute to this unwanted variability. This frequently is a source of errors, rescans, and inefficient workflows in MR imaging, making it all the more important that MRI scanners deliver reliable and reproducible image data irrespective of the patient being examined or the person operating the system. This issue is precisely addressed with the new BioMatrix technology.

BioMatrix sensors in the table automatically track a patient’s respiratory pattern, giving users insights into a patient’s individual ability to hold his or her breath during the scan. This allows the user to select the optimal exam strategy, while also saving time during the examination. BioMatrix tuners can help avoid rescans, which represent a major burden on productivity as well as a driver of additional costs in radiology. In cervical spine examinations, for example, this feature uses intelligent coil technology to automatically set the optimal scan parameters based on the individual patient anatomy, all without any additional user interaction. BioMatrix tuners also improve the quality and reproducibility of whole-body diffusion. Precise control of scan parameters in real-time to match the individual patient anatomy makes it possible to avoid distortions, which can render diffusion imaging non-diagnostic, especially in 3 Tesla MRI. Innovative interfaces also help ensure a consistently high examination quality, accelerating workflows, and improving quality of care. BioMatrix Interfaces accelerate the scanning process by up to 30 percent. Automated patient positioning based on intelligent body models automatically moves the patient table to the correct scan position. An intuitive touchscreen user interface integrated onto the scanner allows for one-touch positioning. A new, easy-to-move motorized patient table further simplifies examinations, especially for adipose, immobile, and trauma patients.

Magnetom Vida is the first system to be equipped with the new BioMatrix technology, designed to tackle the challenges of variability and thereby, reduce unwanted variability in MRI examinations. It will help users achieve fewer rescans, predictable scheduling, and consistent, high-quality personalized examination results.
The ability to provide consistent and reproducible quality regardless of the individual patient and user will help reduce rescans, which can be a great financial burden for healthcare institutions. As publications have shown, rescans can account for up to €100,000 per year and system in additional costs.

Professor Konstantin Nikolaou, Medical Director of the Department of Diagnostic and Interventional Radiology at University Hospital Tübingen considers Magnetom Vida to be part of the general trend toward precision medicine: “To provide our patients with individual therapies, we need every piece of information available. When it comes to imaging, this means that we need robust, standardized, and reproducible image data that are always of the same quality regardless of the patient or user. Only then we can compare results and link them with additional information, such as data from laboratory medicine or genetics,” says Nikolaou, referring to the clinical validation of the new MRI scanner in his department. “Magnetom Vida gives us this data quality and comprehensive image information so that we can choose the right kind of personalized therapy and evaluate it – to see, for instance, how a patient responds to chemotherapy before tumour removal. This MRI scanner along with BioMatrix technology is the perfect fit for our current medical approaches, and is helping us on our way to quantitative radiology,” says Nikolaou.

Faster scans with very high patient comfort
Magnetom Vida has another major advantage: “We can examine sick patients faster with Magnetom Vida,” says Professor Mike Notohamiprodjo who, as head of MRI at University Hospital Tübingen, works intensively with the new scanner. “The scanner offers the highest degree of patient comfort with the performance of a research system, which speeds up our workflows,” he says. As examinations in Tübingen show, the new scanner decreases measurement times for musculoskeletal and prostate imaging compared to previous MRI systems. What is more, it does so with significantly improved image quality: “The signal-to-noise ratio in the clinical images is up to 30 percent higher than with systems from the previous generation,” says Notohamiprodjo.

While this is partly due to BioMatrix technology, it is also a result of the diverse insights that developers at Siemens Healthineers gathered from intense fundamental research and close customer collaborations. Key learnings from the development of a 7-Tesla research MRI system translated into a new 3-Tesla magnet design. Magnetom Vida’s all-new system architecture offers extremely high performance and unmet long-term stability – without requiring any more space than previous clinical systems. The new scanner’s 60/200 XT gradient system provides over 2.7 megawatts of power, making it the most powerful commercially available gradients in a 70-centimeter bore scanner. And, thanks to a very large field of view (55x55x50 cm), Magnetom Vida can also cover larger body regions in one step, such as full coverage abdominal exams.

The result is a great increase in productivity for routine examinations of the brain, spine, and joints – from correct patient positioning at the touch of a button to transferring the clinical images to the PACS archiving system. This is made possible by the GO technologies, which automate and simplify workflows from the start of the scan right through to the quality control of the image data. A new user interface allows not only for automated acquisition and processing, but also for more advanced post-processing applications to run at the scanner. With spine examinations, for instance, GO technologies reduce the time needed by about a fifth. This means that a department could carry out four additional spine examinations per day and per system. Given the decline in reimbursement rates, this is of great value to many radiological institutes.

Broader patient groups and new clinical growth areas
The system also allows customers to access additional clinical growth fields – for instance, by serving patient groups that were previously deemed unsuitable for MRI due to issues such as cardiac arrhythmias, excess weight, or health problems that prevent them from actively supporting the scan. With the introduction of Magnetom Vida, Siemens Healthineers expands its Compressed Sensing applications – which can make MRI scans up to ten times faster – to cover more body regions. It features Compressed Sensing Cardiac Cine, which allows free-breathing cardiology examinations (even when using contrast medium for comprehensive tissue characterization). Now, Compressed Sensing Grasp-Vibe, which enables dynamic, free-breathing liver examinations in one comprehensive scan by the push of button and for every patient, is also available. Until today, in contrast, dynamic liver imaging required four steps with exhausting breath-holds and complex timing. Grasp-Vibe technology also makes the post-processing of liver images significantly faster. During the studies he carried out in Tübingen, Professor Notohamiprodjo found that post-processing times fell from 20 to just four minutes.

Magnetom Vida even simplifies whole-body scans, which are currently particularly challenging, because they have to cover multiple scan sections and demand highly trained users. A new special technology, the Whole-Body Dot Engine, allows these difficult scans to be carried out in predictable time slots, as short as 25 minutes, with very high quality. This is accomplished through intelligent automation. The planning and execution of the scan requires only a few simple clicks. Providing high-quality diffusion weighted imaging is important for whole body exams; Magnetom Vida, with its BioMatrix Tuner technology, can deliver this distortion-free. Combined also with its strong 60/200 gradients and a large homogeneous field of view, Magnetom Vida makes whole-body examinations simple to perform, reproducibly, and with very high-quality. This is a major advantage, particularly when treating oncology patients, such as those with multiple myeloma, where guidelines have recently been moving toward whole-body MRI scans for therapy control.

Magnetom Vida offers not only numerous clinical advances, but also a number of improvements in energy consumption. These help to lower the total cost of ownership of the system over its entire life-cycle. Technologies such as Eco-Power provide an intelligent control of power-hungry components by switching them off when they are not needed for longer periods of time. The result is a MR scanner that consumes 30 percent less energy than the industry average for 3-Tesla scanners, as reported by the European Coordination Committee of the radiological, electromedical and healthcare IT industry (COCIR). 

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Scientific literature review – pathology

Improvements in cell block processing: The Cell-Gel method

La Fortune KA, Randolph ML, Wu HH, Cramer HM. Cancer 2017; 125(4): 267–276

BACKGROUND: The ability to produce adequate cell blocks profoundly impacts the diagnostic usefulness of cytology specimens. Cell blocks are routinely processed from fine-needle aspiration specimens or concentrated fluid samples. Obtaining directed passes for the sole purpose of producing a cell block is common practice, particularly when the cytopathologist anticipates the need for ancillary immunocytochemical stains and/or molecular studies.
METHODS: The authors developed an effective and inexpensive process for producing cell blocks that consistently yields abundant cellular material, which they have termed the Cell-Gel method. This method can be simplified into 3 main steps: (1) preparing the sample; (2) constructing the cell block; and (3) processing the cell block. Highlights of the protocol include using a hemolytic fixative for sample preparation and disposable base moulds for cell block construction.
RESULTS: The cell block failure rate in the current study decreased from 18% with the HistoGel Tube method (January 2014 – December 2014) to 6% with the Cell-Gel method (January 2015 – December 2016). The authors evaluated 110 cell blocks processed with the HistoGel Tube method and 110 cell blocks processed with the Cell-Gel method, for a total evaluation of 220 cell blocks.
CONCLUSIONS: The authors have developed an effective and inexpensive protocol for producing cell blocks that consistently yields abundant cellular material. The Cell-Gel method uses a hemolytic fixative and disposable base moulds to produce adequate cell blocks. When the method was implemented, the cell block failure rate of the study laboratory decreased by approximately 67%.

Lung carcinoma predictive biomarker testing by immunoperoxidase stains in cytology and small biopsy specimens: advantages and limitations

Zhou F, Moreira AL. Arch Pathol Lab Med 2016; 140(12): 1331–1337

CONTEXT: In the burgeoning era of molecular genomics, immunoperoxidase (IPOX) testing grows increasingly relevant as an efficient and effective molecular screening tool. Patients with lung carcinoma may especially benefit from the use of IPOX because most lung carcinomas are inoperable at diagnosis and only diagnosed by small tissue biopsy or fine-needle sampling. When such small specimens are at times inadequate for molecular testing, positive IPOX results still provide actionable information.
OBJECTIVE: To describe the benefits and pitfalls of IPOX in the detection of biomarkers in lung carcinoma cytology specimens and small biopsies by summarizing the currently available commercial antibodies, pre-analytic variables, and analytic considerations.
DATA SOURCES: PubMed.
CONCLUSIONS: Commercial antibodies exist for IPOX detection of aberrant protein expression due to EGFR L858R mutation, EGFR E746_A750 deletion, ALK rearrangement, ROS1 rearrangement, and BRAF V600E mutation, as well as PD-L1 expression in tumour cells. Automated IPOX protocols for ALK and PD-L1 detection were recently approved by the Food and Drug Administration as companion diagnostics for targeted therapies, but consistent interpretive criteria remain to be elucidated, and such protocols do not yet exist for other biomarkers. The inclusion of cytology specimens in clinical trials would expand patients’ access to testing and treatment, yet there is a scarcity of clinical trial data regarding the application of IPOX to cytology, which can be attributed to trial designers’ lack of familiarity with the advantages and limitations of cytology. The content of this review may be used to inform clinical trial design and advance IPOX validation studies.

DUX4 immunohistochemistry is a highly sensitive and specific marker for CIC-DUX4 fusion-positive round cell tumor

Siegele B, Roberts J, Black JO, Rudzinski E et al. Am J Surg Pathol 2017; 41(3): 423–429

The histologic differential diagnosis of pediatric and adult round cell tumours is vast and includes the recently recognized entity CIC-DUX4 fusion-positive round cell tumour. The diagnosis of CIC-DUX4 tumour can be suggested by light microscopic and immunohistochemical features, but currently, definitive diagnosis requires ancillary genetic testing such as conventional karyotyping, fluorescence in situ hybridization, or molecular methods. We sought to determine whether DUX4 expression would serve as a fusion-specific immunohistochemical marker distinguishing CIC-DUX4 tumour from potential histologic mimics. A cohort of CIC-DUX4 fusion-positive round cell tumours harbouring t(4;19)(q35;q13) and t(10;19)(q26;q13) translocations was designed, with additional inclusion of a case with a translocation confirmed to involve the CIC gene without delineation of the partner. Round cell tumours with potentially overlapping histologic features were also collected. Staining with a monoclonal antibody raised against the C-terminus of the DUX4 protein was applied to all cases. DUX4 immunohistochemistry exhibited diffuse, crisp, strong nuclear staining in all CIC-DUX4 fusion-positive round cell tumours (5/5, 100% sensitivity), and exhibited negative staining in nuclei of all of the other tested round cell tumours, including 20 Ewing sarcomas, 1 Ewing-like sarcoma, 11 alveolar rhabdomyosarcomas, 9 embryonal rhabdomyosarcomas, 12 synovial sarcomas, 7 desmoplastic small round cell tumours, 3 malignant rhabdoid tumours, 9 neuroblastomas, and 4 clear cell sarcomas (0/76, 100% specificity). Thus, in our experience, DUX4 immunostaining distinguishes CIC-DUX4 tumours from other round cell mimics. We recommend its use when CIC-DUX4 fusion-positive round cell tumour enters the histologic differential diagnosis.


Role of quantitative p16INK4A mRNA assay and digital reading of p16INK4A immunostained sections in diagnosis of cervical intraepithelial neoplasia

Vasiljević N, Carter PD, Reuter C et al. Int J Cancer 2017; 141(4): 829–836

Visual interpretation of cervical biopsies is subjective and variable, generally showing fair to moderate inter-reader agreement in distinguishing high from low grade cervical intraepithelial neoplasia (CIN). We investigated the performance of two objective p16 quantitative tests in comparison with visual assessment: (i) p16-mRNA assay and (ii) digital analysis of sections stained for p16 protein. The primary analysis considered 232 high-risk human papilloma virus positive (HPV+) samples from diagnostic cervical specimens. A p16 RT-qPCR (p16-mRNA assay) was run on mRNA extracted from formalin-fixed paraffin-embedded sections. Two p16 immunohistochemistry (IHC) readings, a visual read by a histopathologist (Visual IHC) and a digital read of a high-resolution scan (Digital IHC), were done on adjacent sections. The worst reviewed CIN grade (agreed by at least two histopathologists) from up to two biopsies and a loop excision was taken, with CIN2/3 as the primary endpoint. Visual IHC attained a specificity of 70% (95%CI 61–77) for 85% (95%CI 77–91%) sensitivity. The four-point Visual IHC staining area under the curve (AUC) was 0.77 (95%CI 0.71–0.82), compared with 0.71 (95%CI 0.64–0.77) for p16-mRNA and 0.67 (95%CI 0.60–0.74) for Digital IHC. Spearman rank-order correlations were: visual to p16-mRNA 0.41, visual to digital 0.49 and p16-mRNA to digital: 0.22. The addition of p16-mRNA assay to visual reading of p16 IHC improved the AUC from 0.77 to 0.84 (P=0.0049). p16-mRNA testing may be complementary to visual IHC p16 staining for a more accurate diagnosis of CIN, or perhaps a substitute in locations with a lack of skilled pathologists.

Biomarkers for pathology diagnosis of uterine cervix malignant glandular lesions

Lee S, Rose MS, Sahasrabuddhe VV et al. Int J Gynecol Pathol 2017;36(4): 310–322

Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the published data. This systematic review and meta-analysis was performed to investigate the sensitivity and specificity of immunohistochemistry biomarkers in the tissue-based diagnosis of cervical adenocarcinoma histotypes compared with normal endocervix and benign glandular lesions. The systematic review and meta-analysis used a PICOT framework and QUADAS-2 to evaluate the quality of included studies. The literature search spanned 40 years and ended June 30, 2015. Abstracts of identified records were independently screened by two of the authors who then conducted a full-text review of selected articles. Sensitivity and specificity of immunohistochemistry expression in malignant glandular lesions of the cervix classified per WHO 2003 compared with 5 benign comparators (normal/benign endocervix, and benign endocervical, endometrioid, gastric, and mesonephric lesions) were calculated. Of 902 abstracts screened, 154 articles were selected for full review. Twenty-five articles with results for 36 biomarkers were included. The only biomarker with enough studies for a meta-analysis was p16 and the definition of positive p16 staining among them was variable. Nevertheless, any positive p16 expression was sensitive, ranging from 0.94 to 0.98 with narrow confidence intervals (CIs), for adenocarcinoma in situ (AIS) and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical and endometrioid lesions. Specificity for AIS and mucinous adenocarcinomas was also high with narrow CIs compared with benign endocervical lesions. The specificity was high for AIS, 0.99 (0.24, 1.0), and mucinous adenocarcinoma, 0.95 (0.52, 1.0), compared with normal/benign endocervix but with wider CIs, and low with very wide CIs compared with benign endometrioid lesions: 0.31 (0.00, 0.99) and 0.34 (0.00, 0.99), respectively. Results from single studies showed that p16, p16/Ki67 dual stain, ProExC, CEA, ESA, HIK1083, Claudin 18, and ER loss in perilesional stromal cells were useful with high (≥0.75) sensitivity and specificity estimates in ≥1 malignant versus benign comparisons. None of the biomarkers had highly useful sensitivity and specificity estimates for AIS, mucinous adenocarcinomas, or minimal deviation adenocarcinoma/gastric adenocarcinoma compared with benign gastric or mesonephric lesions or for mesonephric carcinoma compared with normal/benign endocervix, benign endocervical, endometrial, or mesonephric lesions. Any expression of p16 supports a diagnosis of AIS and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical lesions. The majority of studies did not separate mosaic/focal p16 staining from diffuse staining as a distinct pattern of p16 overexpression and this may have contributed to the poor performance of p16 in distinguishing AIS and mucinous adenocarcinomas from benign endometrioid lesions. Single studies support further investigation of 8 additional biomarkers that have highly useful sensitivity and specificity estimates for ≥1 malignant glandular lesions compared with ≥1 of the 5 benign comparators.

GATA3 expression in triple-negative breast cancers

Byrne DJ, Deb S, Takano EA, Fox SB. Histopathology 2017; 71(1): 63–71

AIMS: GATA-binding protein 3 (GATA3) is a well-studied transcription factor found to be essential in the development of luminal breast epithelium and has been identified in a variety of tumour types, including breast and urothelial carcinomas, making it a useful immunohistochemistry marker in the diagnosis of both primary and metastatic disease.
METHODS AND RESULTS: We investigated GATA3 protein expression in a 106 primary triple-negative breast carcinomas (100 basal-like, six non-basal-like) using Cell Marque mouse monoclonal anti-GATA3 (L50-823). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to quantify mRNA expression in 22 triple-negative breast cancers (TNBCs) (20 primary and two cell lines), four luminal (three primary and one cell line) and five human epidermal growth factor receptor 2 (HER2) (four primary and one cell line) amplified tumours. In 98 TNBCs where IHC was assessable, 47 (48%) had a 1+ or greater staining with 20 (21%) having high GATA3 expression when using a weighted scoring.
CONCLUSION: Our study has demonstrated that GATA3 expression is common in primary triple-negative breast carcinomas. It also suggests that although GATA3 is an estrogen receptor (ER) regulated gene, it still proves useful in differentiating between primary and metastatic tumours in patients with a history of breast cancer regardless of its molecular subtype.

Accuracy of fine needle cytology in histological prediction of papillary thyroid carcinoma variants: a prospective study

Cipolletta Campanile A, Malzone MG, Losito NS et al. 2017; 28(3): 187–197

Fine needle cytology (FNC) is a crucial procedure in the preoperative diagnosis of thyroid tumours. Papillary thyroid carcinoma (PTC), in its classic variant (cPTC), is the most common malignant neoplasm of the thyroid. Several histological variants of PTC have been described, each one with its own characteristics and prognosis. The ability of FNC to identify the variants represents a challenge even for a skilled pathologist. The aim of this study was to evaluate the diagnostic cytological accuracy of FNC in PTC and to look for specific features that could predict the different variants. This was a single centre prospective study on 128 patients who received a diagnosis of PTC on FNC. The smears were blindly reviewed by two cytopathologists to create a frequency score (0, 1, 2, 3) of the features for each variant. The cytological parameters were divided into three groups: architectural, nucleo-cytoplasmic, and background features. Univariate analysis was performed by chi-square test with Yates correction and Fisher exact test as appropriate. Multiple regression analysis was performed among the variables correlated at the linear correlation. The correlation study between cytology and histology showed an accuracy of FNC in classic, follicular, and oncocytic PTC variants of 63.5, 87.5, and 87%, respectively. Familiarity with cytological features may allow an early diagnosis of a given PTC variant on FNC samples. This is fundamental in a preoperative evaluation for the best surgical approach and subsequent treatment.

Mindray: a world class company grown in China

Founded in 1991, Mindray is one of the leading global providers of medical devices, committed to innovation in the fields of patient monitoring & life support, in-vitro diagnostics, and medical imaging. International Hospital’s editor in chief met David Yin, Group Vice President and General Manager of International Sales and Marketing on the Mindray stand and reviewed their latest products on display at CMEF.
Headquartered in Shenzhen, China, Mindray possesses a global marketing and service network with subsidiaries and branch offices in 32 countries in North and Latin America, Europe, Africa and Asia-Pacific, as well as 31 branch offices in China. To date, Mindray has 7,600 employees. Particularly strong is its R&D department which employs 1,700 engineers and accounts for a spend of almost 10% of annual revenue. The company is dedicated to adopting advanced technologies and transforming them into accessible innovation, improving the quality of care, while helping to reduce its cost and make it more accessible to a larger part of humanity. Today, Mindray’s products and services can be found in healthcare facilities in over 190 countries besides China.
Mindray is the perfect example of a company built on growth from the domestic to the international market. Key milestones in its development include the New York Stock Exchange listing in 2006, the Datascope acquisisition in 2008 and the Zonare takeover of 2014.
Among the many products on show at CMEF was the cutting edge design BeneVision patient monitor with its rotatable landscape and portrait layout as well as its innovative clinical decision support tools like HemoSight. On the ultrasound imaging side, the Resona 6 premium system was developed with Zonare and is powered by the innovative ZONE Sonography Technology. At the other end, the M6 hand-carried ultrasound system offers a wide range of tools that maximize diagnostic capabilities at the bedside. Another highlight at CMEF was the WATO EX65 Pro anesthesia workstation which is newly launched in the Chinese market.

Kimes, March 15-18 2018, Seoul, Korea

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