Evaluation of PEG-coated iron oxide nanoparticles as blood pool tracers for preclinical magnetic particle imaging.

Superparamagnetic iron oxide (SPIO) nanoparticles with optimized and well-characterized properties are critical for Magnetic Particle Imaging (MPI). MPI is a novel in vivo imaging modality that promises to integrate the speed of X-ray CT, safety of MRI and sensitivity of PET. Since SPIOs are the source of MPI signal, both the core and surface properties must be optimized to enable efficient in vivo imaging with pharmacokinetics tailored for specific imaging applications. Existing SPIOs like Resovist (ferucarbotran) provide a suboptimal MPI signal, and further limit MPI's in vivo utility due to rapid systemic clearance. An SPIO agent with a long blood half-life (t1/2) would be a versatile MPI tracer with widespread applications. Here we show that a long circulating polyethylene glycol (PEG)-coated SPIO tracer, LS-008, provides excellent colloidal stability and a persistent intravascular MPI signal, showing its potential as the first blood pool tracer optimized for MPI. We evaluated variations of PEG coating and found that colloidal stability of tracers improved with the increasing PEG molecular weight (keeping PEG loading constant). Blood circulation in mice, evaluated using Magnetic Particle Spectrometry (MPS), showed that the t1/2 of SPIO tracers varied with both PEG molecular weight and loading. LS-008, coated with 20 kDa PEG at 18.8% loading capacity, provided the most promising long-term colloidal stability with a t1/2 of about 105 minutes in mice. In vivo MPI imaging with LS-008 using a 7 T/m/µ0 3D x-space MPI mouse scanner revealed a prolonged intravascular signal (3-5 hours) post-injection. Our results show the optimized magnetic properties and long systemic retention of LS-008 making it a promising blood pool MPI tracer, with potential to enable MPI imaging in cardio- and cerebrovascular disease models, and solid tumor quantification and imaging via enhanced permeation and retention.

Study of tumour cellularity in locally advanced breast carcinoma on neo-adjuvant chemotherapy.

BACKGROUND: Breast cancer is the most common invasive malignancy which occurs in women worldwide. The advent of neoadjuvant chemotherapy has radically changed the management of locally advanced breast cancer and a complete response is reported to significantly improve disease free survival. Traditionally, clinical response is assessed on basis of tumour size. In this study, an attempt was made to check whether tumour cellularity could be a better prognostic factor and also to check as to what impact the correlation of tumour size with cellularity had on the response assessment in locally advanced breast cancer patients. MATERIALS AND METHODS: Thirty seven patients with locally advanced breast cancer, who were treated by neoadjuvant chemotherapy during the period of December 2008 to May 2009, were selected for the study and from their case records, tumour size, clinical response and demographic details were gathered. Tumour cellularity was assessed prior to chemotherapy in core needle biopsy sections and it was matched with that seen in subsequent mastectomy specimens. Tumour size and cellularity were then correlated with the different treatment response groups and they were statistically analyzed by using the SPSS, version 13.0 software. RESULTS: After neoadjuvant chemotherapy, the tumour size and cellularity were found to be significantly reduced in breast carcinomas (p<0.05, paired t-test). The relative changes in cellularity which were seen were highly variable between individual patients and different clinical response groups, particularly in the partial response and no response categories. The product of cellularity and size dramatically changed the distribution of residual tumour pathology, thus causing a shift towards a complete response. CONCLUSION: The current study showed that the product of tumour size and cellularity may be a better prognostic indicator of clinical response in patients with neoadjuvant chemotherapy treated locally advanced breast cancer and that it would enable a new definition for clinical response in the future.

Hip resurfacing revision rates: radiological audit of risk factors.

INTRODUCTION: We performed a retrospective radiological audit of the hip resurfacings carried out in our trust over a five-year period. Abnormal cup inclination angle (CIA) and stem shaft angle (SSA) are recognised risk factors for revision in hip resurfacing. Our aims were to identify the CIA and SSA for hip resurfacings in our trust, to determine the revision rate in a CIA of ≥60° and an SSA of >0° varus, thereby identifying a high risk group for close, long-term follow up. METHODS: A total of 247 patients underwent hip resurfacing in our trust between April 2003 and March 2008. The CIA and SSA were recorded. Of the 247 patients, 26 were excluded as there were no appropriate radiographs and so results were analysed for 221 patients. RESULTS: The mean CIA was 47.6°. Over a third of the patients (34%) had a CIA of >50° and 13% had >60°. The mean SSA was 1.4° varus. Over two-thirds of the patients (67%) had a varus SSA. There were six revisions but one was excluded as it was secondary to infection. The revision rate was 10% in patients with a CIA of ≥60° and 1% in those with a CIA of <60° (p=0.017), and 1% in a varus and 4% in a valgus SSA ((p)>0.05) respectively. CONCLUSIONS: The measurement of the CIA and SSA in hip resurfacings has identified a high risk group for close long-term follow up. There is already a 10% revision rate in those patients with a CIA of >60°. Hip resurfacing may generate a large revision burden in the 'average' surgeon's hands and all hospitals/surgeons should review their radiological outcomes critically and identify those at risk of revision.

The position of the centre of the distal radial articular surface in the sagittal plane: a radiological study.

Using a digital vernier calliper, measurements of the position of the centre of the distal radial articular surface in the sagittal plane with respect to the long axis of the distal radius were made on 50 lateral radiographs of normal wrists. In all 50 cases, the centre of the distal radial articular surface was palmar on the long axis of the radius. The mean value for this palmar position was 5.3mm (44% of the radial shaft width). There was no correlation between the position of the centre of the distal radial articular surface and either the width of the radial shaft, the length of the articular surface of the distal radius or the age or sex of the individuals. However, the position of the centre of rotation was found to correlate with palmar tilt. The palmar position of the centre of the distal radial articular surface on the long axis of the radius may be biomechanically important.

Palmar cortical angle of the distal radius: a radiological study.

Fifty lateral radiographs of normal wrists were viewed to determine the palmar cortical angle of the distal radius. The palmar cortical angle is different to its previously described palmar tilt or angulation. The mean value for the palmar cortical angle was 37 degrees (range, 26-50 degrees). This may be clinically important in the design of palmar plates for the distal radius.