Nondestructive analysis of urinary calculi using micro computed tomography

BACKGROUND: Micro computed tomography (micro CT) has been shown to provide exceptionally high quality imaging of the fine structural detail within urinary calculi. We tested the idea that micro CT might also be used to identify the mineral composition of urinary stones non-destructively. METHODS: Micro CT x-ray attenuation values were measured for mineral that was positively identified by infrared microspectroscopy (FT-IR). To do this, human urinary stones were sectioned with a diamond wire saw. The cut surface was explored by FT-IR and regions of pure mineral were evaluated by micro CT to correlate x-ray attenuation values with mineral content. Additionally, intact stones were imaged with micro CT to visualize internal morphology and map the distribution of specific mineral components in 3-D. RESULTS: Micro CT images taken just beneath the cut surface of urinary stones showed excellent resolution of structural detail that could be correlated with structure visible in the optical image mode of FT-IR. Regions of pure mineral were not difficult to find by FT-IR for most stones and such regions could be localized on micro CT images of the cut surface. This was not true, however, for two brushite stones tested; in these, brushite was closely intermixed with calcium oxalate. Micro CT x-ray attenuation values were collected for six minerals that could be found in regions that appeared to be pure, including uric acid (3515 – 4995 micro CT attenuation units, AU), struvite (7242 – 7969 AU), cystine (8619 – 9921 AU), calcium oxalate dihydrate (13815 – 15797 AU), calcium oxalate monohydrate (16297 – 18449 AU), and hydroxyapatite (21144 – 23121 AU). These AU values did not overlap. Analysis of intact stones showed excellent resolution of structural detail and could discriminate multiple mineral types within heterogeneous stones. CONCLUSIONS: Micro CT gives excellent structural detail of urinary stones, and these results demonstrate the feasibility of identifying and localizing most of the common mineral types found in urinary calculi using laboratory CT

An exploration of men's experiences of undergoing active surveillance for favourable-risk prostate cancer: A mixed methods study protocol

BACKGROUND: Prostate cancer is one of the most common male cancers worldwide. Active Surveillance (AS) has been developed to allow men with lower risk disease to postpone or avoid the adverse side effects associated with curative treatments until the disease progresses. Despite the medical benefits of AS, it is reported that living with untreated cancer can create a significant emotional burden for patients. METHODS/DESIGN: The aim of this study is to gain insight into the experiences of men eligible to undergo AS for favourable-risk PCa. This study has a mixed-methods sequential explanatory design consisting of two phases: quantitative followed by qualitative. Phase 1 has a multiple point, prospective, longitudinal exploratory design. Ninety men diagnosed with favourable-risk prostate cancer will be assessed immediately post-diagnosis (baseline) and followed over a period of 12 months, in intervals of 3 month. Ninety age-matched men with no cancer diagnosis will also be recruited using peer nomination and followed up in the same 3 month intervals. Following completion of Phase 1, 10-15 AS participants who have reported both the best and worst psychological functioning will be invited to participate in semi-structured qualitative interviews. Phase 2 will facilitate further exploration of the quantitative results and obtain a richer understanding of participants' personal interpretations of their illness and psychological wellbeing. DISCUSSION: To our knowledge, this is the first study to utilise early baseline measures; include a healthy comparison group; calculate sample size through power calculations; and use a mixed methods approach to gain a deeper more holistic insight into the experiences of men diagnosed with favourable-risk prostate cancer

Molecular MRI of Inflammation in Atherosclerosis

Inflammatory activity in atherosclerotic plaque is a risk factor for plaque rupture and atherothrombosis and may direct interventional therapy. Inflammatory activity can be evaluated at the (sub)cellular level using in vivo molecular MRI. This paper reviews recent progress in contrast-enhanced molecular MRI to visualize atherosclerotic plaque inflammation. Various MRI contrast agents, among others ultra-small particles of iron oxide, low-molecular-weight Gd-chelates, micelles, liposomes, and perfluorocarbon emulsions, have been used for in vivo visualization of various inflammation-related targets, such as macrophages, oxidized LDL, endothelial cell expression, plaque neovasculature, MMPs, apoptosis, and activated platelets/thrombus. An enzyme-activatable magnetic resonance contrast agent has been developed to study myeloperoxidase activity in inflamed plaques. Agents creating contrast based on the chemical exchange saturation transfer mechanism were used for thrombus imaging. Transfer of these molecular MRI techniques to the clinic will critically depend on the safety profiles of these newly developed magnetic resonance contrast agents

<i>Cis</i> P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae

Induction of the cis form of phosphorylated tau (cis P-tau) has previously been shown to occur in animal models of traumatic brain injury (TBI), and blocking this form of tau using antibody was beneficial in a rodent model of severe TBI. Here the authors show that cis P-tau induction is a feature of several different forms of TBI in humans, and that administration of cis P-tau targeting antibody to rodents reduces or delays pathological features of TBI

Increased endothelial tetrahydrobiopterin synthesis by targeted transgenic GTP-cyclohydrolase I overexpression reduces endothelial dysfunction and atherosclerosis in ApoE-knockout mice.

OBJECTIVE: Increased production of reactive oxygen species and loss of endothelial nitric oxide (NO) bioactivity are key features of vascular disease states such as atherosclerosis. Tetrahydrobiopterin (BH4) is a required cofactor for NO synthesis by endothelial nitric oxide synthase (eNOS); pharmacologic studies suggest that reduced BH4 availability may be an important mediator of endothelial dysfunction in atherosclerosis. We aimed to investigate the importance of endothelial BH4 availability in atherosclerosis using a transgenic mouse model with endothelial-targeted overexpression of the rate-limiting enzyme in BH4 synthesis, GTP-cyclohydrolase I (GTPCH). METHODS AND RESULTS: Transgenic mice were crossed into an ApoE knockout (ApoE-KO) background and fed a high-fat diet for 16 weeks. Compared with ApoE-KO controls, transgenic mice (ApoE-KO/GCH-Tg) had higher aortic BH4 levels, reduced endothelial superoxide production and eNOS uncoupling, increased cGMP levels, and preserved NO-mediated endothelium dependent vasorelaxations. Furthermore, aortic root atherosclerotic plaque was significantly reduced in ApoE-KO/GCH-Tg mice compared with ApoE-KO controls. CONCLUSIONS: These findings indicate that BH4 availability is a critical determinant of eNOS regulation in atherosclerosis and is a rational therapeutic target to restore NO-mediated endothelial function and reduce disease progression

Quantification and 3D reconstruction of atherosclerotic plaque components in apolipoprotein E knockout mice using ex vivo high-resolution MRI.

OBJECTIVE: To investigate the ability of high-resolution MRI to determine composition and microanatomy of atherosclerosis in mouse aortic root and brachiocephalic artery. METHODS AND RESULTS: Aortic root and brachiocephalic arteries of apolipoprotein E knockout (apoE-/-) mice fed Western diet for 10, 20, or 30 weeks were imaged ex vivo (11.7 T; 3D multiecho sequence; resolution 47x47x62.5 microm). Using semiautomated histogram-based methods, MRI accurately quantified lipid-rich/necrotic areas in the aortic root (r2=0.84; P&lt;0.001) and brachiocephalic artery (r2=0.90; P&lt;0.001) compared with histology. Similarly, cell-rich caps in aortic roots, quantified by MRI and histology, correlated closely (r2=0.74; P&lt;0.001). Reconstruction of segmented brachiocephalic arteries in 3D provided unique insights into plaque microanatomy and enabled volumetric quantification of plaque and lipid-rich/necrotic core. Between 10 and 30 weeks, 3D measurement identified an 11.6-fold increase in plaque volume (versus 4.1-fold for 2D) and a 21.3-fold increase in plaque lipid-rich/necrotic core volume (versus 6.4-fold for 2D), indicating superior power of 3D quantification. CONCLUSIONS: Ex-vivo high-resolution 3D MRI accurately quantified lipid-rich/necrotic core and cell-rich cap areas in atherosclerotic lesions in apoE-/- mice. Reconstruction and volumetric quantification of segmented brachiocephalic arteries demonstrated greater sensitivity in detecting changes in plaque size and lipid composition over time than 2D analysis