Quiet PROPELLER MRI Techniques Match the Quality of Conventional PROPELLER Brain Imaging Techniques

BACKGROUND AND PURPOSE:Switching of magnetic field gradients is the primary source of acoustic noise in MR imaging. Sound pressure levels can run as high as 120 dB, capable of producing physical discomfort and at least temporary hearing loss, mandating hearing protection. New technology has made quieter techniques feasible, which range from as low as 80 dB to nearly silent. The purpose of this study was to evaluate the image quality of new commercially available quiet T2 and quiet FLAIR fast spin-echo PROPELLER acquisitions in comparison with equivalent conventional PROPELLER techniques in current day-to-day practice in imaging of the brain.MATERIALS AND METHODS:Thirty-four consecutive patients were prospectively scanned with quiet T2 and quiet T2 FLAIR PROPELLER, in addition to spatial resolution–matched conventional T2 and T2 FLAIR PROPELLER imaging sequences on a clinical 1.5T MR imaging scanner. Measurement of sound pressure levels and qualitative evaluation of relative image quality was performed.RESULTS:Quiet T2 and quiet T2 FLAIR were comparable in image quality with conventional acquisitions, with sound levels of approximately 75 dB, a reduction in average sound pressure levels of up to 28.5 dB, with no significant trade-offs aside from longer scan times.CONCLUSIONS:Quiet FSE provides equivalent image quality at comfortable sound pressure levels at the cost of slightly longer scan times. The significant reduction in potentially injurious noise is particularly important in vulnerable populations such as children, the elderly, and the debilitated. Quiet techniques should be considered in these special situations for routine use in clinical practice.

Acoustic noise generated during MR imaging contributes to patient discomfort. Problems associated with high levels of acoustic noise include annoyance, anxiety, and verbal communication difficulties between the patient and operator.^1,2 In addition, the very high noise pressure levels can cause hearing loss. Temporary shifts in hearing thresholds have been reported in 43% of the patients scanned without ear protection and with improperly fitted earplugs.³ In extreme cases, permanent hearing impairment can occur.^3–5 Noise is of particular concern in populations vulnerable to hearing loss such as the very young and elderly and those who may not be able to manage the effectiveness of earplug placement such as patients with psychiatric disorders or reduced levels of consciousness.⁵ Fetal noise exposure is also a concern.⁶The primary source of acoustic noise in MR imaging procedures is the pulsed currents generated in gradient coils for spatial encoding of the MR signal.⁷ These currents, in the presence of the strong static magnetic field of the MR imaging system, induce significant (Lorentz) forces that cause vibrations in the gradient coils, which, in turn, generate a compression wave in the air perceived as the scanner noise.^8–10 Previous methods used to ameliorate the high acoustic noise levels of clinical MR imaging include acoustic insulation of the scanner bore, resulting in reduced bore diameter and gradient waveform shaping/filtering^11,12; bandwidth limiting¹³; and restricting gradient performance—each trading image quality and acquisition speed for only modest noise reduction. More recent studies have demonstrated that innovative pulse-sequence modifications can be applied to achieve substantial reductions of acoustic noise while maintaining image quality. Novel, almost silent sequences have recently become available.^14–17 Before these new techniques can be widely adopted, validation against traditional techniques must be performed.In this study, we evaluated the image quality of new commercially available quiet T2 PROPELLER (Q-T2) and quiet T2 FLAIR PROPELLER (Q-FLAIR) sequences in comparison with our standard of care conventional T2 PROPELLER (C-T2) and T2 FLAIR PROPELLER (C-FLAIR) techniques. To our knowledge, this is the first study to assess the performance of quiet T2 and quiet T2 FLAIR MR imaging applications in day-to-day clinical practice.     

Elevated plasma sVCAM-1 levels in children with sickle cell disease: impact of chronic transfusion therapy

Vascular cell adhesion molecule-1 (VCAM-1) has been implicated as being important in the pathophysiology of acute pain episodes (APE) and acute chest syndrome (ACS) of sickle cell disease (SCD). The frequency of these episodes is reduced by chronic transfusion therapy. The impact of chronic transfusion therapy on VCAM-1 expression is unknown. Soluble VCAM-1 (sVCAM-1) levels were measured in plasma using an ELISA assay (R&D Systems) in 61 patients with SCD (age range 1.5-20 years) and 12 normal controls (2.5-14 years). SCD patients included 20 with ACS, 14 with APE, 12 at well-child visits, and 15 receiving chronic transfusion therapy. Asymptomatic SCD patients had higher sVCAM-1 levels compared to normal subjects (P < 0.001). Levels of sVCAM-1 were further elevated during ACS (P < 0.001) and APE (P = 0.072) and returned to the asymptomatic range on resolution. Levels were significantly lower in transfused patients (P = 0.003) compared to asymptomatic SCD patients. Our findings of increased VCAM-1 expression during ACS and perhaps APE offer a rationale for therapeutic use of cytokine and other VCAM-1 modulators. The reduction of sVCAM-1 levels observed in our transfused SCD patients offers insight into the mechanism of the protective effect of transfusion against ACS and APE and possibly stroke.     

Endocarditis and biofilm-associated pili of Enterococcus faecalis

Increasing multidrug resistance in Enterococcus faecalis, a nosocomial opportunist and common cause of bacterial endocarditis, emphasizes the need for alternative therapeutic approaches such as immunotherapy or immunoprophylaxis. In an earlier study, we demonstrated the presence of antibodies in E. faecalis endocarditis patient sera to recombinant forms of 9 E. faecalis cell wall-anchored proteins; of these, we have now characterized an in vivo-expressed locus of 3 genes and an associated sortase gene (encoding sortase C; SrtC). Here, using mutation analyses and complementation, we demonstrated that both the ebp (encoding endocarditis and biofilm-associated pili) operon and srtC are important for biofilm production of E. faecalis strain OG1RF. In addition, immunogold electron microscopy using antisera against EbpA-EbpC proteins as well as patient serum demonstrated that E. faecalis produces pleomorphic surface pili. Assembly of pili and their cell wall attachment appeared to occur via a mechanism of cross-linking of the Ebp proteins by the designated SrtC. Importantly, a nonpiliated, allelic replacement mutant was significantly attenuated in an endocarditis model. These biologically important surface pili, which are antigenic in humans during endocarditis and encoded by a ubiquitous E. faecalis operon, may be a useful immunotarget for studies aimed at prevention and/or treatment of this pathogen.     

Superior efficacy of co-treatment with dual PI3K/mTOR inhibitor NVP-BEZ235 and pan-histone deacetylase inhibitor against human pancreatic cancer

Genetic alterations activating K-RAS and PI3K/AKT signaling are also known to induce the activity of mTOR kinase through TORC1 and TORC2 complexes in human pancreatic ductal adenocarcinoma (PDAC). Here, we determined the effects of the dual PI3K and mTOR inhibitor, NVP-BEZ235 (BEZ235), and the pan-histone deacetylase inhibitor panobinostat (PS) against human PDAC cells. Treatment with BEZ235 or PS inhibited cell cycle progression with induction of the cell cycle inhibitory proteins, p21 waf1 and p27 kip1. BEZ235 and PS also dose dependently induced loss of cell viability of the cultured PDAC cells, associated with depletion of phosphorylated (p) AKT, as well as of the TORC1 substrates 4EBP1 and p70S6 kinase. While inhibiting p-AKT, treatment with PS induced the levels of the pro-apoptotic proteins BIM and BAK. Co-treatment with BEZ235 and PS synergistically induced apoptosis of the cultured PDAC cells. This was accompanied by marked attenuation of the levels of p-AKT and Bcl-x_L but induction of BIM. Although in vivo treatment with BEZ235 or PS reduced tumor growth, co-treatment with BEZ235 and PS was significantly more effective in controlling the xenograft growth of Panc1 PDAC cells in the nude mice. Furthermore, co-treatment with BEZ235 and PS more effectively blocked tumor growth of primary PDAC heterotransplants (possessing K-RAS mutation and AKT2 amplification) subcutaneously implanted in the nude mice than each agent alone. These findings demonstrate superior activity and support further in vivo evaluation of combined treatment with BEZ235 and PS against PDAC that possess heightened activity of RAS-RAF-ERK1/2 and PI3K-AKT-mTOR pathways.     

A systematic,multidisciplinary approach to address the reproductive needs of HIV-seropositive women

Nearly 130,000 American women are human immunodeficiency virus (HIV) seropositive. The present study sought to establish a comprehensive programme to address their fertility needs in order to minimize infectious, medical and reproductive risks to prospective patients. Forty women, aged 27–42 years, were evaluated. HIV was diagnosed 7.2 ± 0.7 years prior to their seeking care, and most women (n = 38) were on highly active antiretroviral therapy. Their prenatal CD4 counts were 712.2 ± 56 cells/mm³ (range 327–1881) and HIV-1 concentrations were undetectable in all cases prior to initiating treatment. HIV-seropositive women were statistically identical to their age-matched HIV-seronegative counterparts with respect to the IVF clinical outcome parameters measured. Throughout the pregnancies, maternal HIV-1 RNA concentrations remained undetectable and CD4 counts were stable. All infants, tested at birth and at 3 and 6 months of age, remained HIV negative. This is the first report of an institutional paradigm in the USA dedicated to evaluate and treat HIV-seropositive women. Using a multidisciplinary approach to care, HIV-seropositive women may be successfully managed in a programme of assisted reproduction.     

B19 parvovirus infection in children with malignant solid tumors receiving chemotherapy

Two children with rhabdomyosarcoma developed severe anemia following chemotherapy; anemia was more severe compared to that observed following earlier chemotherapy cycles. While one patient had a brisk reticulocytosis, the other had no demonstrable reticulocytes. Both patients had evidence of acute B19 parvovirus infection and subsequently developed appropriate antibody response. A diagnosis of B19 parvovirus infection should be considered in any patient who develops persistent or severe anemia while on chemotherapy. © 1994 Wiley-Liss, Inc.     

Inhibition of growth and regulation of IGFs and VEGF in human prostate cancer cell lines by shikonin analogue 93/637 (SA)

BACKGROUND: Insulin-like growth factors (IGFs) are important mitogens and are involved in normal and malignant cellular proliferation. IGFs and IGF binding proteins (IGFBPs) regulate the prostatic cell growth and reduction/blocking of IGFs has been suggested to be of therapeutic value in prostate cancer. beta,beta-dimethyl acryl shikonin, an extract from the roots of plant Arnebia nobilis has been shown to have anticancer properties but was found to be toxic. Subsequently, several analogoues of beta,beta-dimethyl acryloyl shikonin were synthesized and one of them shikonin analogue 93/637 (SA) was significantly less toxic compared to beta,beta-dimethyl acryloyl shikonin. MATERIALS AND METHODS: We have investigated the effect of SA on prostate cancer cell (DU 145, LNCaP and PC-3) growth and expression of IGFs (IGF-I, IGF-II and IGF-I receptor (IGF-IR)), IGFBP-3 and vascular endothelial growth factor (VEGF). RESULTS: SA had growth inhibitory effect on PC-3 cells in a dose dependent manner. It also showed slight inhibitory effect on the growth of DU 145 and LNCaP cells at low doses ranging from 250 nM to 1 microM and has moderate inhibitory effect at concentrations 2.5 microM and above. Lactate dehydrogenase (LDH) activity assays indicated cellular damage, only at higher concentrations of SA that are greater than 1 microM. Gene expression studies by RT-PCR have demonstrated a decrease in mRNAs of IGF-II in DU 145, IGF-I, and IGF-IR in LNCaP, and IGF-II and VEGF in PC-3 cells and an increase in IGFBP-3 in both DU 145 and PC-3 cells by treatment with SA. CONCLUSIONS: The results demonstrate the inhibitory effect of SA on cellular growth and IGFs specifically in PC-3 cells and suggest a potential therapeutic use in treatment of prostate cancer.     

Duplex Arteriography Prior to Femoral-Popliteal Reconstruction in Claudicants: A Proposal for a New Shortened Protocol

The standard preoperative duplex arteriography (DA) from the aorta to the pedal vessels is time consuming and may be unnecessary in patients presenting with calf claudication alone. The feasibility of a shortened protocol was evaluated. Of 286 femoral-popliteal reconstruction based on DA during the last 4 years, 79 (28%) were primary operations for calf claudication. Eliminating the aortoiliac portion of the test except for the distal external iliac artery and limiting the scanning of the infrapopliteal vessels to one or two arteries in the leg would significantly shorten the exam. To confirm the adequacy of the inflow tract, we relied on the common femoral artery Doppler waveform analysis and the intraoperative graft pressure upon completion of the bypass. Of the 79 primary femoral-popliteal bypasses, 53 (67%) had triphasic common femoral artery waveform and the remaining 26 had monophasic or biphasic waveforms. Three (6%) of the 53 femoral-popliteal bypasses in the former group had significant pressure gradients measured intraoperatively and were treated with iliac angioplasties and stents for unsuspected stenoses in 2 cases and a covered stent for a common iliac aneurysm in 1 case. Three, two, and one infrapopliteal vessel runoff was observed in 24 (45%), 16 (30%), and 9 (17%) extremities, respectively. Four patients (8%) had significant stenoses (>50%) or occlusion of all three infrapopliteal arteries. Eighty-one percent of the patients would have completed the short protocol had we scanned the peroneal artery initially. An additional 8% would have required scanning of a second vessel (anterior tibial) and only 11%, scanning of all three infrapopliteal vessels. The time interval for completion of short-protocol DA was significantly less than the time for the standard DA (16.2 ± 5.2 min vs. 35.1 ± 10.6 min) (p < 0.01). We believe that the proposed short DA protocol combined with intraoperative graft pressure measurements can be used in 94% of the patients who have a patent popliteal artery (â¥7 cm). It is a totally noninvasive approach that is particularly suitable for vascular technologists and surgeons who wish to start utilizing DA instead of contrast arteriography prior to infrainguinal reconstructions. However, the short protocol does not avert the need for completion arteriography of the inflow arteries and readiness to perform endovascular procedures to correct lesions not suspected by common femoral artery waveform analysis.Presented at the 30th Annual Meeting of the Society for Clinical Vascular Surgery, Las Vegas, NV, March 13-17, 2002.