A novel method for the diagnosis of drowning by detection of Aeromonas sobria with PCR method

The acid digestion method has been widely used for the diagnosis of death by drowning, but it is not always sensitive. However, there has been no definitive method to replace acid digestion until now. We speculate that bacteria are more useful markers than plankton for the diagnosis of death by drowning. In this study, from the preserved blood samples of 32 freshwater drowning cases, specific DNA fragments of Aeromonas sobria, one of the most common aquatic bacteria, were examined using PCR. The DNA fragments of the bacterium were detected from 27 of 32 cases with first round PCR or nested-PCR. The remaining 5 cases in which bacterial DNA was not detected had longer storage periods for the blood samples and shorter time intervals from drowning to death. These results indicate that the present method can be applied to the diagnosis of death by drowning.     

Functional MRI with magnetization transfer effects: Determination of BOLD and arterial blood volume changes

The primarily intravascular magnetization transfer (MT)‐independent changes in functional MRI (fMRI) can be separated from MT‐dependent changes. This intravascular component is dominated by an arterial blood volume change (ΔCBV_a) term whenever venous contributions are minimized. Stimulation‐induced ΔCBV_a can therefore be measured by a fit of signal changes to MT ratio. MT‐varied fMRI data were acquired in 13 isoflurane‐anesthetized rats during forepaw stimulation at 9.4T to simultaneously measure blood‐oxygenation‐level–dependent (BOLD) and ΔCBV_a response in somatosensory cortical regions. Transverse relaxation rate change (ΔR₂) without MT was –0.43 ± 0.15 s^?1, and MT ratio decreased during stimulation. ΔCBV_a was 0.46 ± 0.15 ml/100 g, which agrees with our previously‐presented MT‐varied arterial‐spin‐labeled data (0.42 ± 0.18 ml/100 g) in the same animals and also correlates with ΔR₂ without MT. Simulations show that ΔCBV_a quantification errors due to potential venous contributions are small for our conditions. Magn Reson Med 60:1518–1523, 2008. © 2008 Wiley‐Liss, Inc.     

Electrolyte analysis of pleural effusion for discrimination between seawater and freshwater drowning in decomposed bodies

ObjectiveThe diagnosis of drowning is an important issue in forensic investigations. Moreover, discriminating between seawater and freshwater drowning is crucial to identify where the drowning occurred. The present study aimed to investigate electrolyte concentrations in pleural fluid in decomposed bodies in late postmortem intervals and derive cut-off values for the diagnosis of seawater and freshwater drowning.Study designData were collected from 44 seawater drowning cases, 60 freshwater drowning cases, and 30 non-drowning cases with pleural effusion which served as controls. The levels of sodium ion (Na⁺), potassium ion (K⁺), and chloride ion (Cl⁻) of pleural fluid were measured, and two indices were calculated: summation of Na⁺ and K⁺ levels (SUM _Na + K), and summation of Na⁺, K⁺, and Cl⁻ levels (SUM _{Na + K + Cl}). The means of the three ion concentrations and two indices significantly differed between the three groups (p < 0.0001).ResultsThe receiver operating characteristic analysis revealed that the sensitivity and specificity were both 1.000 for SUM _{Na + K + Cl} of 288.3 mEq/L between the seawater and control groups. The Na⁺ value of 109.0 mEq/L also had a high sensitivity of 0.977 and a specificity of 0.933 in the seawater and control groups. The sensitivity and specificity were 0.967 and 1.000, respectively, for SUM _Na + K of 123.2 mEq/L between the freshwater and control groups.ConclusionThe electrolyte concentrations in pleural effusion may be useful for the diagnosis of drowning in decomposed bodies with a longer postmortem interval.     

Hemodynamic analysis of bladder tumors using T1-dynamic contrast-enhanced fast spin-echo MRI

Objectives

To evaluate the hemodynamics of bladder tumors, we developed a method to calculate change in R₁ value (ΔR₁) from T₁-dynamic contrast-enhanced fast spin-echo magnetic resonance imaging (T₁DCE-FSE-MRI).

Materials and methods

On a 1.5-T MR system, T₁DCE-FSE-MRI was performed. This study was applied to 12 patients with urinary bladder tumor, i.e. urothelial carcinoma. We compared ΔR₁–time and ΔSI–time between a peak in the ΔR₁–time and ΔSI–time curve occurred during the first pass within 60 s. Next, we assessed the slope of increase for 180 s after CA injection (Slope_0–180).

Results

The mean slope of the first pass was significantly higher for bladder tumors on both the ΔR₁–time and the ΔSI–time curve compared with normal bladder walls. Moreover, a significant difference was apparent between bladder tumors and normal bladder walls on the mean Slope_0–180 in the ΔR₁-time curve. However, no significant difference in the mean Slope_0–180 was observed on the ΔSI-time curve between bladder tumors and normal bladder walls.

Conclusion

T₁DCE-FSE-MRI offers three advantages: quantitative analysis; high-quality (i.e., artifact-free) images; and high temporal resolution even for SE images. Use of ΔR₁ analysis with T₁DCE-FSE-MRI allows more detailed information on the hemodynamics of bladder tumors to be obtained and assists in differentiation between bladder tumors and the normal bladder wall.     

Measurement of regional blood oxygenation and cerebral hemodynamics

An echo planar linewidth mapping technique, Shufflebutt, has allowed temporal measurements of changes in linewidth caused by static inhomogeneities (ΔLWSI) and transverse relaxation rate (ΔR2) in models of hypoxia and hypercapnia. We demonstrate these changes are due to intravascular susceptibility differences(Δ_X) between the blood and tissue. Contrast agent injections at a /Δ_X equivalent to that of deoxygenatetd blood showed a twofold difference between the contrast agent and physiological anoxia values. Hypercapnia decreased both ΔLWSI and ΔR2 consistent with an increase in blood oxygenation. We attribute these findings to constant oxygen extraction during an increase in blood flow, resulting in less deoxygenated venous blood and thus reduced Δ_X. For in vivoperturbations we found that ΔR/ΔR2′ ≈ 0.33, a ratio much different from that measured in whole blood phantoms (ΔR/ΔR2′ ≈ 2). This demonstrates that signal changes in these studies are produced predominantly by dephasing of extravascular protons due to field inhomogeneities produced by intravascular deoxygenated hemoglobin (deoxyHb).     

Dynamic and simultaneous MR measurement of R1 and R2* changes during respiratory challenges for the assessment of blood and tissue oxygenation

This work presents a novel method for the rapid and simultaneous measurement of R₁ and R₂* relaxation rates. It is based on a dynamic short repetition time steady‐state spoiled multigradient‐echo sequence and baseline R₁ and B₁ measurements. The accuracy of the approach was evaluated in simulations and a phantom experiment. The sensitivity and specificity of the method were demonstrated in one volunteer and in four patients with intracranial tumors during carbogen inhalation. We utilized (ΔR₂*, ΔR₁) scatter plots to analyze the multiparametric response amplitude of each voxel within an area of interest. In normal tissue R₂* decreased and R₁ increased moderately in response to the elevated blood and tissue oxygenation. A strong negative ΔR₂* and ΔR₁ response was observed in veins and some tumor areas. Moderate positive ΔR₂* and ΔR₁ response amplitudes were found in fluid‐rich tissue as in cerebrospinal fluid, peritumoral edema, and necrotic areas. The multiparametric approach was shown to increase the specificity and sensitivity of oxygen‐enhanced MRI compared to measuring ΔR₂* or ΔR₁ alone. It is thus expected to provide an optimal tool for the identification of tissue areas with low oxygenation, e.g., in tumors with compromised oxygen supply. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Value of precontrast T1 for dGEMRIC of native articular cartilage

Purpose

To evaluate if the difference between pre‐ and post‐Gd‐DTPA^2‐ relaxation rate (ΔR₁) provides better differentiation of osteoarthritic patients (OA) from healthy subjects (HS) with dGEMRIC, as compared to post‐Gd‐DTPA^2‐ spin‐lattice relaxation time (T_1Gd).

Materials and Methods

Seventeen OA and 14 HS underwent pre‐ and 90 minutes postcontrast (Gd‐DTPA^2‐) magnetic resonance imaging (MRI) of the knee, using inversion recovery fast spin‐echo and/or Lock–Locker sequences for T₁ mapping. Effect sizes for T_1pre, T_1Gd, and ΔR₁ were calculated, and receiver operating characteristic (ROC) curve and regression analysis were also performed to assess the effectiveness of each parameter in the separation of OA and HS.

Results

T_1Gd and ΔR₁ were almost identical in terms of areas under ROC curves (0.903 and 0.914, respectively), and effect sizes (1.34 and 1.31, respectively). These were significantly higher than T_1pre. In addition, a high inverse correlation was observed between ΔR₁ vs. T_1Gd (R = 0.96).

Conclusion

Either T_1Gd or ΔR₁ could be used as an index in the evaluation of native cartilage. However, considering the practical logistical cost involved in terms of time and effort to acquire precontrast T₁ measurements, our data further support the continued use of T_1Gd as the dGEMRIC index in the evaluation of native cartilage. J. Magn. Reson. Imaging 2009;29:494–497. © 2009 Wiley‐Liss, Inc.     

Temporal changes in the T1 and T2 relaxation rates (ΔR1 and ΔR2) in the rat brain are consistent with the tissue‐clearance rates of elemental manganese

Temporal changes in the T₁ and T₂ relaxation rates (ΔR₁ and ΔR₂) in rat olfactory bulb (OB) and cortex were compared with the absolute manganese (Mn) concentrations from the corresponding excised tissue samples. In vivo T₁ and T₂ relaxation times were measured before, and at 1, 7, 28, and 35 d after intravenous infusion of 176 mg/kg MnCl₂. The values of ΔR₁, ΔR₂, and absolute Mn concentration peaked at day 1 and then declined to near control levels after 28 to 35 d. The Mn bioelimination rate from the rat brain was significantly faster than that reported using radioisotope techniques. The R₁ and R₂ relaxation rates were linearly proportional to the underlying tissue Mn concentration and reflect the total absolute amount of Mn present in the tissue. The in vivo Mn r₁ and r₂ tissue relaxivities were comparable to the in vitro values for aqueous Mn²⁺. These results demonstrate that loss of manganese‐enhanced MRI (MEMRI) contrast after systemic Mn²⁺ administration is due to elimination of Mn²⁺ from the brain. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

The MRI‐measured arterial input function resulting from a bolus injection of Gd‐DTPA in a rat model of stroke slightly underestimates that of Gd‐[14C]DTPA and marginally overestimates the blood‐to‐brain influx rate constant determined by Patlak plots

The hypothesis that the arterial input function (AIF) of gadolinium‐diethylenetriaminepentaacetic acid injected by intravenous bolus and measured by the change in the T₁‐relaxation rate (ΔR₁; R₁ = 1/T₁) of superior sagittal sinus blood (AIF‐I) approximates the AIF of ¹⁴C‐labeled gadolinium‐diethylenetriaminepentaacetic acid measured in arterial blood (reference AIF) was tested in a rat stroke model (n = 13). Contrary to the hypothesis, the initial part of the ΔR₁‐time curve was underestimated, and the area under the normalized curve for AIF‐I was about 15% lower than that for the reference AIF. Hypothetical AIFs for gadolinium‐diethylenetriaminepentaacetic acid were derived from the reference AIF values and averaged to obtain a cohort‐averaged AIF. Influx rate constants (K_i) and proton distribution volumes at zero time (V_p + V_o) were estimated with Patlak plots of AIF‐I, hypothetical AIFs, and cohort‐averaged AIFs and tissue ΔR₁ data. For the regions of interest, the K_is estimated with AIF‐I were slightly but not significantly higher than those obtained with hypothetical AIFs and cohort‐averaged AIF. In contrast, V_p + V_o was significantly higher when calculated with AIF‐I. Similar estimates of K_i and V_p + V_o were obtained with hypothetical AIFs and cohort‐averaged AIF. In summary, AIF‐I underestimated the reference AIF; this shortcoming had little effect on the K_i calculated by Patlak plot but produced a significant overestimation of V_p + V_o. Magn Reson Med 63:1502–1509, 2010. © 2010 Wiley‐Liss, Inc.     

Delayed gadolinium‐enhanced magnetic resonance imaging (dGEMRIC) of hip joint cartilage in femoroacetabular impingement (FAI): Are pre‐ and postcontrast imaging both necessary?

The purpose of this study was to assess if delayed gadolinium MRI of cartilage using postcontrast T₁ (T_1Gd) is sufficient for evaluating cartilage damage in femoroacetabular impingement without using noncontrast values (T₁₀). T_1Gd and ΔR₁ (1/T_1Gd ? 1/T₁₀) that include noncontrast T₁ measurements were studied in two grades of osteoarthritis and in a control group of asymptomatic young‐adult volunteers. Differences between T_1Gd and ΔR₁ values for femoroacetabular impingement patients and volunteers were compared. There was a very high correlation between T_1Gd and ΔR₁ in all study groups. In the study cohort with Tonnis grade 0, correlation (r) was ?0.95 and ?0.89 with Tonnis grade 1 and ?0.88 in asymptomatic volunteers, being statistically significant (P < 0.001) for all groups. For both T_1Gd and ΔR₁, a statistically significant difference was noted between patients and control group. Significant difference was also noted for both T_1Gd and ΔR₁ between the patients with Tonnis grade 0 osteoarthritis and those with grade 1 changes. Our results prove a linear correlation between T_1Gd and ΔR₁, suggesting that T_1Gd assessment is sufficient for the clinical utility of delayed gadolinium MRI of cartilage in this setting and additional time‐consuming T₁₀ evaluation may not be needed. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Trans-lesional fractional flow reserve gradient as derived from coronary CT improves patient management: ADVANCE registry

BackgroundThe role of change in fractional flow reserve derived from CT (FFR_CT) across coronary stenoses (ΔFFR_CT) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown.ObjectivesTo investigate the incremental value of ΔFFR_CT in predicting early revascularization and improving efficiency of catheter laboratory utilization.MaterialsPatients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFR_CT was measured 2 ?cm distal to stenosis. ΔFFR_CT was manually measured as the difference of FFR_CT across visible stenosis.ResultsOf 4730 patients (66 ?± ?10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFR_CT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26–1.35]; p ?< ?0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFR_CT. Among the 3 models (model 1: risk factors ?+ ?stenosis type and location ?+ ?CAD-RADS; model 2: model 1 ?+ ?FFR_CT; model 3: model 2 ?+ ?ΔFFR_CT), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86–0.88] vs 0.85 [0.84–0.86]; p ?< ?0.001), with the greatest incremental value for FFR_CT 0.71–0.80. ΔFFR_CT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFR_CT ≤0.8, a diagnostic strategy incorporating ΔFFR_CT >0.13, would potentially reduce ICA by 32.2% (1638–1110, p ?< ?0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%.ConclusionsΔFFR_CT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFR_CT, particularly for those with FFR_CT 0.71–0.80. ΔFFR_CT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization.     

Quantitative analysis of liver function using superparamagnetic iron oxide- and Gd-EOB-DTPA-enhanced MRI: comparison with Technetium-99m galactosyl serum albumin scintigraphy

Purpose

To examine whether or not the parameters regarding the signal intensity of the liver parenchyma on superparamagnetic iron oxide (SPIO)- and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI are correlated with the parameters of Technetium-99m galactosyl serum albumin (^99mTc-GSA) scintigraphy.

Materials and methods

This retrospective study consisted of 55 and 33 patients who underwent SPIO- and Gd-EOB-DTPA-enhanced MRI in addition to ^99mTc-GSA scintigraphy, respectively. For each patient, we calculated Pre R2* and Pre R2, which are equivalent to R2* (=1/T2*) and R2 (=1/T2) values of the liver parenchyma; ΔR2* and ΔR2, which represent differences in R2* and R2 values of the liver parenchyma before and after administration of SPIO; and the increase rates of both the liver-to-spleen signal intensity ratio (LSR) and the liver-to-major psoas muscle signal intensity ratio (LMR) on the hepatobiliary phase compared with the precontrast image. For ^99mTc-GSA scintigraphy, the receptor index LHL15 and the blood clearance index HH15 were recorded.

Results

Regression analysis showed a moderate correlation between Pre R2* and LHL15 (P < 0.05). Mild to moderate correlations were also obtained between any combination of ΔR2* and ΔR2 on the one hand, and LHL15 and HH15 on the other (P < 0.05). There were moderate correlations between any combination of increase rates of LSR and LMR on the one hand, and LHL15 and HH15 on the other (P < 0.05–0.001).

Conclusion

Pre R2*, ΔR2*, ΔR2 and the increase rates of LSR and LMR could be used as quantitative indicators of liver function.     

Investigating temporal fluctuations in tumor vasculature with combined carbogen and ultrasmall superparamagnetic iron oxide particle (CUSPIO) imaging

A combined carbogen ultrasmall superparamagnetic iron oxide (USPIO) imaging protocol was developed and applied in vivo in two murine colorectal tumor xenograft models, HCT116 and SW1222, with established disparate vascular morphology, to investigate whether additional information could be extracted from the combination of two susceptibility MRI biomarkers. Tumors were imaged before and during carbogen breathing and subsequently following intravenous administration of USPIO particles. A novel segmentation method was applied to the image data, from which six categories of R₂* response were identified, and compared with histological analysis of the vasculature. In particular, a strong association between a negative ΔR₂*_carbogen followed by positive ΔR₂*_USPIO with the uptake of the perfusion marker Hoechst 33342 was determined. Regions of tumor tissue where there was a significant ΔR₂*_carbogen but no significant ΔR₂*_USPIO were also identified, suggesting these regions became temporally isolated from the vascular supply during the experimental timecourse. These areas correlated with regions of tumor tissue where there was CD31 staining but no Hoechst 33342 uptake. Significantly, different combined carbogen USPIO responses were determined between the two tumor models. Combining ΔR₂*_carbogen and ΔR₂*_USPIO with a novel segmentation scheme can facilitate the interpretation of susceptibility contrast MRI data and enable a deeper interrogation of tumor vascular function and architecture. Magn Reson Med 66:227–234, 2011. © 2011 Wiley‐Liss, Inc.     

Drowning, haemodilution, haemolysis and staining of the intima of the aortic root-- preliminary observations

In order to demonstrate that hyponatraemia due to haemodilution occurs within the left ventricle following freshwater drowning, and to determine whether lysed blood resulting from left ventricular haemodilution may cause staining of the aortic intima, the following studies were undertaken. Measurements of left ventricular sodium levels were performed in 74 consecutive coronial cases where death was attributed to drowning, consisting of 44 and 30 deceased who were believed to be victims of freshwater and saltwater drowning, respectively. Left ventricular sodium levels differed significantly between the two groups (p<0.001), with a range of 93-147 mmol/L in freshwater drowning (mean=117+/-14.2 mmol/L) and 123-183 in saltwater drowning (mean=153+/-14.4 mmol/L). In addition, the mean sodium level of 117 mmol/L in freshwater drowning was significantly lower than the standard range of 137-145 mmol/L. In a second study, portions of aorta and pulmonary trunk from a euthanised pig were soaked in lysed blood resulting in marked haemolytic staining of the intima of both vessels after 20 min. Water and a mixture of blood and water were then injected into the left ventricles in two further pig carcasses, respectively, resulting in haemolytic staining of the intima of the aortic roots, with no staining of the pulmonary trunks. These studies have confirmed that significant hyponatraemia secondary to haemodilution may occur within the left ventricle in freshwater drowning, and that haemolysed blood is capable of causing staining of the aortic root in an animal model. These results provide further data to support haemolytic staining of the aortic root intima as a possible manifestation of freshwater drowning.     

Integrated 18F-FDG PET/perfusion CT for the monitoring of neoadjuvant chemoradiotherapy in rectal carcinoma: correlation with histopathology

Purpose

The aim of this study was to prospectively monitor changes in the flow-metabolic phenotype (ΔFMP) of rectal carcinoma (RC) after neoadjuvant chemoradiotherapy (CRT) and to evaluate whether ΔFMP of RC correlate with histopathological prognostic factors including response to CRT.

Methods

Sixteen patients with RC (12 men, mean age 60.7?±?12.8 years) underwent integrated ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/perfusion CT (PET/PCT), followed by neoadjuvant CRT and surgery. In 13 patients, PET/PCT was repeated after CRT. Perfusion [blood flow (BF), blood volume (BV), mean transit time (MTT)] and metabolic [maximum and mean standardized uptake values (SUV_max, SUV_mean)] parameters as well as the FMP (BF × SUV_max) were determined before and after CRT by two independent readers and correlated to histopathological prognostic factors of RC (microvessel density, necrosis index, regression index, vascular invasion) derived from resected specimens. The diagnostic performance of ΔFMP for prediction of treatment response was determined.

Results

FMP significantly decreased after CRT (p?<?0.001), exploiting higher changes after CRT as compared to changes of perfusion and metabolic parameters alone. Before CRT, no significant correlations were found between integrated PET/PCT and any of the histopathological parameters (all p?>?0.05). After CRT, BV and SUV_max correlated positively with the necrosis index (r?=?0.67/0.70), SUV_max with the invasion of blood vessels (r?=?0.62) and ΔFMP with the regression index (r?=?0.88; all p?<?0.05). ΔFMP showed high accuracy for prediction of histopathological response to CRT (AUC 0.955, 95 % confidence interval 0.833–1.000, p?<?0.01) using a cut-off value of ?75 %.

Conclusion

In RC, ΔFMP derived from integrated ¹⁸F-FDG PET/PCT is useful for monitoring the effects of neoadjuvant CRT and allows prediction of histopathological response to CRT.     

Dynamic hysteresis between gradient echo and spin echo attenuations in dynamic susceptibility contrast imaging

Perfusion measurements using dynamic susceptibility contrast imaging provide additional information about the mean vessel size of microvasculature when supplemented with a dual gradient echo (GE) – spin echo (SE) contrast. Dynamic increase in the corresponding transverse relaxation rate constant changes, ΔR_2GE and ΔR_2SE, forms a loop on the (Δ, ΔR_2GE) plane, rather than a reversible line. The shape of the loop and the direction of its passage differentiate between healthy brain and pathological tissue, such as tumour and ischemic tissue. By considering a tree model of microvasculature, the direction of the loop is found to be influenced mainly by the relative arterial and venous blood volume, as well as the tracer bolus dispersion. A parameter Λ is proposed to characterize the direction and shape of the loop, which might be considered as a novel imaging marker for describing the pathology of cerebrovascular network. Magn Reson Med 69:981–991, 2013. © 2012 Wiley Periodicals, Inc.     

A new screening method to detect proximal dental caries using fluorescence imaging

ObjectivesThis study aimed to assess the screening performance of the quantitative light-induced fluorescence (QLF) technology to detect proximal caries using both fluorescence loss and red fluorescence in a clinical situation. Moreover, a new simplified QLF score for the proximal caries (QS-Proximal) is proposed and its validity for detecting proximal caries was evaluated as well.MethodsThis clinical study included 280 proximal surfaces, which were assessed by visual-tactile and radiographic examinations and scored by each scoring system according to lesion severity. The occlusal QLF images were analysed in two different ways: (1) a quantitative analysis producing fluorescence loss (ΔF) and red fluorescence (ΔR) parameters; and (2) a new QLF scoring index. For both quantitative parameters and QS-Proximal, the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) were calculated as a function of the radiographic scoring index at the enamel and dentine caries levels.ResultsBoth ΔF and ΔR showed excellent AUROC values at the dentine caries level (ΔF = 0.860, ΔR = 0.902) whereas a relatively lower value was observed at the enamel caries level (ΔF = 0.655, ΔR = 0.686). The QS-Proximal also showed excellent AUROC ranged from 0.826 to 0.864 for detecting proximal caries at the dentine level.ConclusionThe QS-Proximal, which represents fluorescence changes, showed excellent performance in detecting proximal caries using the radiographic score as the gold standard.     

Synthesis and evaluation of new imaging agent for central nicotinic acetylcholine receptor α7 subtype

IntroductionThe nicotinic acetylcholine receptor (nAChR) α7 subtype (α₇ nAChR) is one of the major nAChR subtypes in the brain. We synthesized C-11 labeled α₇ nAChR ligands, (R)-2-[¹¹C]methylamino-benzoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester ([¹¹C](R)-MeQAA) and its isomer (S)-[¹¹C]MeQAA, for in vivo investigation with positron emission tomography (PET). Then, the potential of (R)- and (S)-[¹¹C]MeQAA for in vivo imaging of α₇ nAChR in the brain was evaluated in mice and monkeys.MethodsThe binding affinity for α₇ nAChR was measured using rat brain. Biodistribution and in vivo receptor blocking studies were undertaken in mice. Dynamic PET scans were performed in conscious monkeys.ResultsThe affinity for α₇ nAChR was 41 and 182 nM for (R)- and (S)-MeQAA, respectively. The initial uptake in the mouse brain was high ([¹¹C](R)-MeQAA: 7.68 and [¹¹C](S)-MeQAA: 6.65 %dose/g at 5 min). The clearance of [¹¹C](R)-MeQAA was slow in the hippocampus (α₇ nAChR-rich region) but was rapid in the cerebellum (α₇ nAChR-poor region). On the other hand, the clearance was fast for [¹¹C](S)-MeQAA in all regions. The brain uptake of [¹¹C](R)-MeQAA was decreased by methyllycaconitine (α₇ nAChR antagonist) treatment. In monkeys, α₇ nAChRs were highly distributed in the thalamus and cortex but poorly distributed in the cerebellum. The high accumulation was observed in the cortex and thalamus for [¹¹C](R)-MeQAA, while the uptake was rather homogeneous for [¹¹C](S)-MeQAA.Conclusions[¹¹C](R)-MeQAA was successfully synthesized and showed high uptake to the brain. However, since the in vivo selectivity for α₇ nAChR was not enough, further PET kinetic analysis or structure optimization is needed for specific visualization of brain α₇ nAChRs in vivo.     

In vivo MRI of fresh stored osteochondral allograft transplantation with delayed gadolinium‐enhanced MRI of cartilage: Protocol considerations and recommendations

The protocol for delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC) was adapted for the evaluation of transplanted osteochondral allograft cartilage. Eight patients with focal grade 4 cartilage defects of the femoral condyle were treated with single cylindrical osteochondral allografts. At 1 and 2 years, dGEMRIC image sequences were acquired and regions of interest (ROIs) were drawn in repair and native control cartilage. Mean T₁ values of region of interest were used to calculate established dGEMRIC metrics. The correlation was measured between the ΔR₁ and R₁‐Post metrics for repair and native cartilage. T₁ times were measured in deep and superficial zones of cartilage. A strong correlation was identified between full‐thickness, deep, and superficial ΔR₁ and R₁‐Post values for native cartilage and repair cartilage for all years (range: 0.893–1.0). The mean T₁ times and ΔR₁ rate between deep and superficial regions of articular cartilage were statistically different for all regions of the distal femora analyzed at 1 year and 2 years after osteochondral allograft transplantation (P < 0.05). The dGEMRIC pre‐Gadolinium scan is unnecessary when evaluating transplanted osteochondral allograft cartilage. The observation of stratified T₁ and ΔR₁ values indicates a need to re‐evaluate the methodology behind the placement of region of interest in dGEMRIC. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.