Non-contrast MRI methods as a tool for the pre-operative assessment and surveillance of the arterio-venous fistula for haemodialysis.

OBJECTIVE: To compare non-contrast enhanced MRI with ultrasound (US) for measurement of arm blood vessel geometries and flow velocities in volunteers and patients with end-stage renal disease. MATERIALS AND METHODS: Subjects were scanned using US (reference standard), and MRI 2D time-of-flight (ToF), 2D phase contrast (PC), and 3D multi-echo data image combination (MEDIC). Patients were also scanned after arteriovenous fistula (AVF) surgery. RESULTS: For mean vessel diameters (radial and brachial arteries; cephalic vein) MEDIC measurements were similar to US (p > 0.05). However, ToF underestimated the mean diameter of the cephalic vein relative to US (p < 0.05). For arterial velocity measurements, the mean values derived by PC-MR and US were similar (p > 0.05). Post-operatively, the intra-luminal signal intensity was hypo-intense at the anastomosis site using ToF and MEDIC. At the same site the outer boundary of the vessel was consistently lost on ToF, but remained clearly delineated on the MEDIC images. DISCUSSION: With the exception of ToF, the MRI data demonstrated excellent agreement with US for measurements of vessel geometry and flow velocity. Further, the ability to clearly delineate the post-surgery vessel edges with MEDIC MRI suggests that the technique may be useful for surveillance after AVF creation or for patient-specific modelling studies.

Case study: technology initiative led to advanced lead optimization screening processes at Bristol-Myers Squibb, 2004-2009.

In this paper, we review the key solutions that enabled evolution of the lead optimization screening support process at Bristol-Myers Squibb (BMS) between 2004 and 2009. During this time, technology infrastructure investment and scientific expertise integration laid the foundations to build and tailor lead optimization screening support models across all therapeutic groups at BMS. Together, harnessing advanced screening technology platforms and expanding panel screening strategy led to a paradigm shift at BMS in supporting lead optimization screening capability. Parallel SAR and structure liability relationship (SLR) screening approaches were first and broadly introduced to empower more-rapid and -informed decisions about chemical synthesis strategy and to broaden options for identifying high-quality drug candidates during lead optimization.

Case study: impact of technology investment on lead discovery at Bristol-Myers Squibb, 1998-2006.

We review strategic approaches taken over an eight-year period at BMS to implement new high-throughput approaches to lead discovery. Investments in compound management infrastructure and chemistry library production capability allowed significant growth in the size, diversity and quality of the BMS compound collection. Screening platforms were upgraded with robust automated technology to support miniaturized assay formats, while workflows and information handling technologies were streamlined for improved performance. These technology changes drove the need for a supporting organization in which critical engineering, informatics and scientific skills were more strongly represented. Taken together, these investments led to significant improvements in speed and productivity as well a greater impact of screening campaigns on the initiation of new drug discovery programs.