Limb functional recovery is impaired in fibroblast growth factor-2 (FGF2) deficient mice despite chronic ischaemia-induced vascular growth.

FGF2 is a potent stimulator of vascular growth; however, even with a deficiency of FGF2 (Fgf2-/-), developmental vessel growth or ischaemia-induced revascularization still transpires. It remains to be elucidated as to what function, if any, FGF2 has during ischaemic injury. Wildtype (WT) or Fgf2-/- mice were subjected to hindlimb ischaemia for up to 42 days. Limb function, vascular growth, inflammatory- and angiogenesis-related proteins, and inflammatory cell infiltration were assessed in sham and ischaemic limbs at various timepoints. Recovery of ischaemic limb function was delayed in Fgf2-/- mice. Yet, vascular growth response to ischaemia was similar between WT and Fgf2-/- hindlimbs. Several angiogenesis- and inflammatory-related proteins (MCP-1, CXCL16, MMPs and PAI-1) were increased in Fgf2-/- ischaemic muscle. Neutrophil or monocyte recruitment/infiltration was elevated in Fgf2-/- ischaemic muscle. In summary, our study indicates that loss of FGF2 induces a pro-inflammatory microenvironment in skeletal muscle which exacerbates ischaemic injury and delays functional limb use.

The role of proximal versus distal stomach resection in the weight loss seen after vertical sleeve gastrectomy.

The mechanisms involved in the weight loss seen after vertical sleeve gastrectomy (VSG) are not clear. The rat stomach has two morphologically and functionally distinct proximal and distal parts. The rat model for VSG involves complete removal of the proximal part and 80% removal of the distal part along the greater curvature. The purpose of this study was to understand the potential independent contributions of removal of these distinct gastric sections to VSG outcomes. We prepared four surgical groups of male Long-Evans rats: VSG, sham surgery (control), selective proximal section removal (PR), and selective distal section removal (DR). Gastric emptying rate (GER) was highest after VSG compared with all other groups. However, PR, in turn, had significantly greater GER compared with both DR and sham groups. The surgery-induced weight loss followed the same pattern with VSG causing the greatest weight loss and PR having greater weight loss compared with DR and sham groups. The results were robust for rats fed regular chow or a high-fat diet. Body mass analysis revealed that the weight loss was due to the loss of fat mass, and there was no change in lean mass after the surgeries. In conclusion, removal of the proximal stomach contributes to most, but not all, of the physiological impact of VSG.

Effects of iodinated contrast on various magnetic resonance imaging sequences and field strength: Implications for characterization of hemorrhagic transformation in acute stroke therapy.

AIM: To characterize the effects of iodinated contrast material (ICM) on magnetic resonance imaging (MRI) comparing different sequences and magnetic fields, with emphasis to similarities/differences with well-known signal characteristics of hemorrhage in the brain. METHODS: Aliquots of iopamidol and iodixanol mixed with normal saline were scanned at 1.5T and 3T. Signal intensity (SI) was measured using similar spin-echo (SE)-T1, SE-T2, gradient-echo (GRE) and fluid-attenuation-inversion-recovery (FLAIR) sequences at both magnets. Contrast to noise ratio (CNR) (SI contrast-SI saline/SD noise) for each aliquot were calculated and Kruskall-wallis test and graphic analysis was used to compare different pulse sequences and ICMs. RESULTS: Both ICM showed increased SI on SE-T1 and decreased SI on SE-T2, GRE and FLAIR at both 1.5T and 3T, as the concentration was increased. By CNR measurements, SE-T2 had the greatest conspicuity at 3T with undiluted iopamidol (92.6 ± 0.3, P < 0.00) followed by iodixanol (77.5 ± 0.9, P < 0.00) as compared with other sequences (CNR range: 15-40). While SE-T2 had greatest conspicuity at 1.5T with iopamidol (49.3 ± 1, P < 0.01), SE-T1 showed similar or slightly better conspicuity (20.8 ± 4) than SE-T2 with iodixanol (23 ± 1.7). In all cases, hypo-intensity on GRE was less conspicuous than on SE-T2. CONCLUSION: Iodixanol and iopamidol shorten T1 and T2 relaxation times at both 1.5T and 3T. Hypo-intensity due to shortened T2 relaxation time is significantly more conspicuous than signal changes on T1-WI, FLAIR or GRE. Variations in signal conspicuity according to pulse sequence and to type of ICM are exaggerated at 3T. We postulate T2 hypointensity with less GRE conspicuity differentiates ICM from hemorrhage; given the well-known GRE hypointensity of hemorrhage. Described signal changes may be relevant in the setting of recent intra-arterial or intravenous ICM administration in translational research and/or human stroke therapy.

Radiation Dose to the Breast by 64-slice CT: Effects of Scanner Model and Study Protocol.

RATIONALE AND OBJECTIVES: This work aimed to study the effects of scanner model and study protocol on radiation dose received by breast tissues from 64-slice computed tomography (CT) studies. MATERIALS AND METHODS: Four scanner models and three study protocols were used in scanning an anthropomorphic phantom with breast modules. Each protocol follows recommendations or guidelines from the American Association of Physicists in Medicine and the American College of Radiology. Twenty thermoluminescent dosimeters were placed inside the breast modules to measure breast tissue doses. Both the absolute and the normalized breast tissue doses were analyzed. RESULTS: The mean glandular doses of a lung cancer screening CT, a chest/abdomen/pelvis CT, and a virtual colonoscopy CT are equivalent to less than 1, 5-7, and 1-3 two-view digital mammograms, respectively, for a standard-sized patient. The normalized breast dose differs significantly (P < 0.01) between lung cancer screening CT and chest/abdomen/pelvis CT; however, it shows less than ±10% variation among scanner models for the same protocol. In virtual colonoscopy CT, breast tissue dose decreases with the distance between local tissues to the edge of the x-ray field, although the decreasing trend varies for different scanner models and protocol settings. CONCLUSIONS: When breasts are entirely included in the primary x-ray field, breast dose by 64-slice CT is mainly protocol dependent, with the normalized breast dose about 15% lower for protocols with modulated mA than for those with constant mA; when breasts are only partially included in the primary beam field, breast dose by 64-slice CT is dependent on both the scanner model and the protocol settings.

In vivo optical imaging of brain tumors and arthritis using fluorescent SapC-DOPS nanovesicles.

We describe a multi-angle rotational optical imaging (MAROI) system for in vivo monitoring of physiopathological processes labeled with a fluorescent marker. Mouse models (brain tumor and arthritis) were used to evaluate the usefulness of this method. Saposin C (SapC)-dioleoylphosphatidylserine (DOPS) nanovesicles tagged with CellVue Maroon (CVM) fluorophore were administered intravenously. Animals were then placed in the rotational holder (MARS) of the in vivo imaging system. Images were acquired in 10° steps over 380°. A rectangular region of interest (ROI) was placed across the full image width at the model disease site. Within the ROI, and for every image, mean fluorescence intensity was computed after background subtraction. In the mouse models studied, the labeled nanovesicles were taken up in both the orthotopic and transgenic brain tumors, and in the arthritic sites (toes and ankles). Curve analysis of the multi angle image ROIs determined the angle with the highest signal. Thus, the optimal angle for imaging each disease site was characterized. The MAROI method applied to imaging of fluorescent compounds is a noninvasive, economical, and precise tool for in vivo quantitative analysis of the disease states in the described mouse models.

Consequence of use of lower dose flat plate fluoroscopy in pediatric patients undergoing ablation for supraventricular tachycardia.

Traditional imaging for ablation of supraventricular tachycardia has been fluoroscopy, although 3-dimensional electroanatomic mapping (3D) has been demonstrated to reduce radiation exposure. This study compares a technique for the reduction of radiation, low-dose fluoroscopy (LD), with standard-dose fluoroscopy (SD) and 3D with SD (3D-SD). This was a single institutional retrospective cohort study. All patients undergoing initial ablation for atrioventricular reentrant tachycardia (AVRT) or atrioventricular nodal reentrant tachycardia (AVNRT) from 2009 to 2012 were reviewed and divided into 3 groups: (1) SD, (2) 3D (CARTO or NavX) with SD, or (3) LD. LD uses the same equipment as SD but includes customized changes to the manufacturer's lowest settings by decreasing the requested dose to the detector. Primary outcomes were fluoroscopy time and dose area product exposure. One hundred eighty-one patients were included. The median age was 15.0 years (3.3-20.8); 59% had AVRT, 35% had AVNRT, and 6% had both AVRT and AVNRT. LD decreased the dose area product (DAP) compared with SD (637.0 vs 960.1 cGy*cm², p = 0.01) with no difference in fluoroscopy time. 3D-SD decreased fluoroscopy time compared with SD (9.9 vs 18.3 minutes, p <0.001) with DAP of 570.1.0 versus 960.1 cGy*cm² (p = 0.16). LD and 3D-SD had comparable DAP (637.0 vs 570.1 cGy*cm², p = 0.67), even though LD had significantly longer fluoroscopy time (19.9 vs 9.9 minutes, p <0.001). In conclusion, LD during catheter ablation of AVRT and AVNRT significantly reduced the DAP compared with SD and had similar radiation exposure compared with 3D with SD.

Minimizing nuclear medicine technologist radiation exposure during 131I-MIBG therapy.

131I-metaiodobenzylguanidine is a norepinephrine analog that concentrates in adrenergic tissue and has been shown to be an effective radiotherapeutic agent used to treat tumors of neural crest origin, particularly neuroblastoma, a sympathetic nervous system malignancy of children. The purpose of this study was to determine the radiation dose received by nuclear medicine technologists while preparing and administering 131I-metaiodobenzylguanidine therapy dosages, and if any changes could be implemented that would reduce a technologist's dose. The study involves the collection of total whole body doses received by technologists during the treatment of six patients. Patient dosages ranged from 9.25 to 31.1 GBq, with radiation exposures to the nuclear medicine technologists averaging 0.024 µSv per MBq administered to the patient. Subsequently, the doses received by the technologists were analyzed with respect to specific process steps performed during 131I-metaiodobenzylguanidine therapy including package receipt, dosage preparation, and dosage administration. Results show that the largest contribution to the technologist's whole body radiation dose (>83%) is received during the dosage administration process step. After additional shielding was installed for use during the dosage administration process step, technologists' doses decreased 80%.

Atypical brain torque in boys with developmental stuttering.

The counterclockwise brain torque, defined as a larger right prefrontal and left parietal-occipital lobe, is a consistent brain asymmetry. Reduced or reversed lobar asymmetries are markers of atypical cerebral laterality and have been found in adults who stutter. It was hypothesized that atypical brain torque would be more common in children who stutter. Magnetic resonance imaging-based morphology measures were completed in boys who stutter (n = 14) and controls (n = 14), ages 8-13. The controls had the expected brain torque configurations whereas the boys who stutter were atypical. These results support the hypothesis that developmental stuttering is associated with atypical prefrontal and parietal-occipital lobe asymmetries.

Assessment of aggressiveness of prostate cancer: correlation of apparent diffusion coefficient with histologic grade after radical prostatectomy.

OBJECTIVE: The purpose of this article is to evaluate the relationship between apparent diffusion coefficient (ADC) values, tumor volume, and total Gleason grade in patients with prostate cancer before radical prostatectomy. MATERIALS AND METHODS: A total of 110 patients with prostate cancer who had undergone endorectal prostate MRI at 1.5 T before radical prostatectomy were included. ADC values were derived by drawing a region of interest on the histologically confirmed tumors. Tumor volume was obtained by manual segmentation on T2-weighted images (T2WIs) and ADC maps. The relationship between the ADC value or tumor volume and the Gleason grade was assessed by using multivariate mixed linear and effect models. Multivariate analysis was performed to evaluate the accuracy of ADC and tumor volume in determining the aggressiveness of prostate cancer. RESULTS: A total of 197 tumors were studied; 128 (65%) tumors were found in the peripheral zone and 69 (35%) were found in the central gland. The ADC value was found to be negatively correlated with the Gleason grade (r = -0.39 for peripheral zone cancer). Higher ADC values were found to be associated with lower Gleason grades in the peripheral zone prostate cancers. No association was found in the central zone prostate cancers. Both ADC values and tumor volumes were found to significantly predict tumor aggressiveness, specifically in the peripheral zone (area under the curve, 0.78). CONCLUSION: ADC values were found to be negatively correlated with the postsurgical Gleason grade in patients with prostate cancer. Our results show that ADC values might help to predict prostate cancer, especially for tumors in the peripheral zone. Given the substantial overlap in the ADC values, the addition of other MR parameters, such as volumetry, and technical improvements in diffusion-weighted imaging might improve accuracy in the stratification of patients.

Relevance of subcortical stroke in dysphagia.

BACKGROUND AND PURPOSE: Unilateral cortical lesions are associated with dysphagia in ischemic stroke. It is unclear, however, whether acute subcortical stroke is associated with a similar risk of dysphagia. The aim of this study was to determine the occurrence of dysphagia in purely subcortical stroke and identify dysphagia characteristics. METHODS: Between 2003 and 2005, videofluoroscopic swallow studies (VFSSs) were completed in 20 consecutive ischemic stroke patients with purely subcortical lesions (right hemisphere damage [RHD]=10, left hemisphere damage [LHD]=10) and 25 age-matched controls. Individuals were classified with dysphagia when at least 2 swallowing measures were 2 standard deviations above mean scores for the control group. Lesion volume, hemisphere, and location were determined from diffusion-weighted magnetic resonance imaging scans. RESULTS: Seven subcortical stroke patients (35%) met VFSS criteria for dysphagia (LHD=5, RHD=2); 4 patients presented with clinically significant dysphagia. A significant interaction between hemisphere and lesion location was identified. Whereas 3 of 5 patients with dysphagia (60%) had lesions to the left periventricular white matter (PVWM), LHD patients without dysphagia did not have PVWM lesions. In contrast, no RHD patients with PVWM lesions had dysphagia, and 6 of 8 patients without dysphagia (75%) had PVWM lesions. Oral transfer was significantly slower in patients with subcortical stroke compared with the healthy adults. CONCLUSIONS: Lesions to the left PVWM may be more disruptive to swallowing behavior than similar lesions to the right PVWM. Swallowing deficits involving oral control and transfer may be a marker of subcortical neural axis involvement.

Morphometry of human insular cortex and insular volume reduction in Williams syndrome.

Functional imaging in humans and anatomical data in monkeys have implicated the insula as a multimodal sensory integrative brain region. The topography of insular connections is organized by its cytoarchitectonic regions. Previous attempts to measure the insula have utilized either indirect or automated methods. This study was designed to develop a reliable method for obtaining volumetric magnetic resonance imaging (MRI) measurements of the human insular cortex, and to validate that method by examining the anatomy of insular cortex in adults with Williams syndrome (WS) and healthy age-matched controls. Statistical reliability was obtained among three raters for this method, supporting its reproducibility not only across raters, but within different software packages. The procedure described here utilizes native-space morphometry as well as a method for dividing the insula into connectivity-based sub-regions estimated from cytoarchitectonics. Reliability was calculated in both ANALYZE (N=3) and BrainImageJava (N=10) where brain scans were measured once in each hemisphere by each rater. This highly reliable method revealed total, anterior, and posterior insular volume reduction bilaterally (all p's<.002) in WS, after accounting for reduced total brain volumes in these participants. Although speculative, the reduced insular volumes in WS may represent a neural risk for the development of hyperaffiliative social behavior with increased specific phobias, and implicate the insula as a critical limbic integrative region. Native-space quantification of the insula may be valuable in the study of neurodevelopmental or neuropsychiatric disorders related to anxiety and social behavior.

fMRI characterization of the language formulation area.

Participants read sentences presented one word at a time, half of which ended with a semantically incongruent ending. 1.5T functional magnetic resonance imaging data were collected from 11 participants, showing that the left posterior inferior temporal region, which has previously been termed the Language Formulation Area (LFA), responded to cloze probability. It is suggested, based on anatomical positioning and a literature review, that the responsiveness of the LFA to cloze probabilities may reflect a role in coordinating the lexical and non-lexical reading pathways. Finally, it is noted that previous studies have implicated this region in dyslexia and some speculations are made in this regard.

PET/CT and SPECT/CT dosimetry in children: the challenge to the pediatric imager.

Both positron emission tomography (PET) and computed tomography (CT) contribute significantly to the effective dose from PET/CT imaging. For PET imaging, the effective dose is related to the administered activity and age of patient. For CT, there are many factors that determine effective dose. Effective dose is dependent on tube current (mA), tube potential (kVp), rotation speed, pitch, slice thickness, patient mass, and the exact volume of the patient that is being imaged. The CT scan may be acquired at exposure parameters similar to those used for diagnostic CT, but more commonly, the tube current is reduced and a localization CT scan of somewhat less than optimal diagnostic quality is obtained. A very low dose CT scan for attenuation correction may also be considered.

Anatomical asymmetries of anterior perisylvian speech-language regions.

Anterior cortical perisylvian areas important for speech and language functions include the pars triangularis (PTR), comprised of heteromodal association cortex, and the pars opercularis (POP), comprised of motor association cortex. The anatomy of these frontal language regions has not been well studied in large samples, however in smaller samples, leftward asymmetry of these regions has been found. Sex-linked differences have also been suggested, with bilateral activation of frontal language areas in women and leftward activation in men. We used volumetric MRI methods to measure the gray matter volume of the PTR, POP, and diagonal sulcus (DS) in 60 healthy right-handed adults and examined the distribution of asymmetry of these regions. Sex-linked differences in volume and asymmetry of anterior speech regions were also examined. For the PTR, there was a slight leftward asymmetry, however for the POP+DS, there was a slight rightward asymmetry. The DS was present slightly more often in the right hemisphere than in the left hemisphere and its frequency was similar in men and women. There were no significant sex-linked differences in volume or asymmetry for any of these frontal areas. More studies are necessary, looking at the anatomy of anterior language regions in large samples and examining the relationship between anatomy and function.

Lobar asymmetries in subtypes of dyslexic and control subjects.

Reading involves phonologic decoding, in which readers "sound out" a word; orthographic decoding, in which readers recognize a word visually, as in "sight reading"; and comprehension. Because reading can involve multiple processes, dyslexia might be a heterogeneous disorder. This study investigated behavior and gross lobar anatomy in subtypes of dyslexic and control subjects. Subjects aged 18 to 25 years with identified reading problems and a group of healthy controls were given cognitive and behavioral tests and volumetric brain magnetic resonance imaging (MRI). Because atypical cerebral laterality has been proposed as a potential neural risk for dyslexia, dyslexic and control subjects were compared on anatomy of gross lobar regions. On asymmetry quotients, no significant differences were found between groups. Examination of the percentage of total brain volume of each structure revealed that control and dyslexic subjects were significantly different (P = .018). Dyslexic subjects had a larger percentage of brain volume than did the controls in the areas of total prefrontal (P = .003; 9.30% larger) and superior prefrontal (P = .004; 11.48% larger region). A Pearson correlation was performed to investigate whether a relationship existed between behavioral measures and either volumes of total prefrontal and total occipital regions or asymmetry quotients. A significant positive relationship between the left total occipital and word identification performance existed (R = .452, P = .045). Because it is believed by some that dyslexia occurs in varying degrees of severity, and because one of the research questions in this study is whether anatomy relates to severity or to distinct biologic groups, subjects were grouped according to both the nature and distinct pattern of reading or language performance and the degree of deficit. A battery of reading tests revealed five clinical subgroups of control (two) and dyslexic (three) subjects. These subgroups were statistically different on all cognitive and behavioral measures. When asymmetry was investigated across subgroups, significant differences between subgroups were found at the multivariate level (P = .043). Only the phonologic deficit groups (weak phonologic controls, phonologic deficit dyslexic subjects) had atypical asymmetry patterns. This finding suggests that lack of subtyping could have confounded earlier studies and that anomalous asymmetry might be related to phonologic dyslexia, whereas other subtypes might be reflective of environmental factors. Examination of volume at the subgroup level also showed differences between subgroups that might have implications for the nature of compensation. This study supports the concept that anomalous anatomy might reflect anomalous functional cerebral laterality, which could be a risk factor for developmental dyslexia, varying according to the nature of the deficit.

Variability in perisylvian brain anatomy in healthy adults.

Gray matter volumes of Heschl's gyrus (HG), planum temporale (PT), pars triangularis (PTR), and pars opercularis were measured on MRI in 48 healthy right-handers. There was the expected leftward PT asymmetry in 70.8%, and leftward PTR asymmetry in 64.6% of the sample. When asymmetry patterns within individuals were examined, there was not one typical pattern, rather several typical configurations were found. In addition, some combinations of asymmetry did not exist in our sample suggesting that some perisylvian anatomical configurations may provide a more suitable neural substrate for the development of language than others. There were also sex differences in HG. Men had rightward asymmetry and women demonstrated leftward asymmetry, due to women having smaller right HG, compared to men.

Sex-linked differences in the anatomy of the perisylvian language cortex: a volumetric MRI study of gray matter volumes.

Perisylvian regions important for auditory processing include Heschl's gyrus (HG), the planum temporale (PT), the posterior superior temporal gyrus (pSTG), and the posterior ascending ramus (PAR). Sex-linked differences in language functions and anatomy have been suggested. To examine sex-linked differences, the authors used MRI to measure HG, PT, pSTG, and PAR volumes. Sex differences were found in right HG and right pSTG volumes but not in the left volumes of these structures. For the PT, there were sex differences in asymmetry; women exhibited leftward asymmetry of the PT, whereas men did not exhibit PT asymmetry. These findings suggest that there are sex-linked differences in the anatomy of primary and association auditory cortices.

Brain metabolite concentration ratios in vivo: multisite reproducibility by single-voxel 1H MR spectroscopy.

Ten normal subjects were scanned identically at three separate sites (Little Rock, Houston, and New Orleans) to evaluate the reproducibility of brain metabolite ratios in single-voxel (1)H point-resolved spectroscopy sequence (PRESS) magnetic resonance (MR) spectroscopy in vivo. All scans were processed by a single individual at a single site. Coefficients of variation of the measured metabolite ratios generally were in the range found for previous single-voxel, single-site reproducibility studies. No differences were found among the sites for ratios of N-acetylaspartate to creatine (NAA/Cr) or choline to Cr (Cho/Cr) in left thalamus by multivariate ANOVA. Metabolite ratios of Cr or Cho relative to local brain H(2)O did not vary among the sites. However, by multivariate ANOVA, NAA/H(2)O differed between Little Rock and New Orleans, but not between those sites and Houston. Intraclass correlation coefficients suggested reasonable reproducibility between Little Rock and New Orleans, but not between those sites and Houston.