The Clinical Impact of Accurate Cystine Calculi Characterization Using Dual-Energy Computed Tomography.

Dual-energy computed tomography (DECT) has recently been suggested as the imaging modality of choice for kidney stones due to its ability to provide information on stone composition. Standard postprocessing of the dual-energy images accurately identifies uric acid stones, but not other types. Cystine stones can be identified from DECT images when analyzed with advanced postprocessing. This case report describes clinical implications of accurate diagnosis of cystine stones using DECT.

Radiation Dose Reduction in Dual-Energy CT: Does It Affect the Accuracy of Urinary Stone Characterization?

OBJECTIVE: The purpose of this article is to assess the effect of radiation dose reduction in dual-energy CT (DECT) on the performance of renal stone characterization using a patient cohort. MATERIALS AND METHODS: CT data from 39 unenhanced DECT examinations performed for stone characterization were retrospectively analyzed in this study. Reduced-dose images were simulated at 75%, 50%, and 25% of the routine dose using a previously validated noise-insertion algorithm. Differentiation between uric acid (UA) and non-UA stones was performed using a fixed cutoff value for the dual-energy ratio. ROC analysis was performed to determine optimal cutoff values and the associated sensitivity and specificity. RESULTS: Of the 206 stones found, 43 were UA and 163 were non-UA. The mean (± SD) volume CT dose index (CTDIvol) was 16.0 ± 4.0 mGy at the 100% dose level. The mean noise in 100-kV images increased from 40.9 ± 6.8 HU at 100% dose to 46.8 ± 8.8 HU, 57.7 ± 12.5 HU, and 85.4 ± 22.9 HU at 75%, 50%, and 25% dose levels, respectively. Using the default cutoff value, for stones 10 mm(3) or larger, the sensitivity/specificity were 100.0%/98.8%, 82.8%/98.8%, and 89.3%/98.7%, at 75%, 50%, and 25% dose levels, respectively. ROC analysis showed varying optimal cutoff values at different dose levels. The sensitivity and specificity improved with use of these optimal cutoff values. Differentiation capability decreased for stones smaller than 10 mm(3). CONCLUSION: At 75% of the 16-mGy routine dose, the sensitivity and specificity for differentiating UA from non-UA stones were minimally affected for stones 10 mm(3) or larger. The use of optimal cutoff values for dual-energy ratio as dose decreased (and noise increased) provided improved performance.

The critical role of membralin in postnatal motor neuron survival and disease.

Hitherto, membralin has been a protein of unknown function. Here, we show that membralin mutant mice manifest a severe and early-onset motor neuron disease in an autosomal recessive manner, dying by postnatal day 5-6. Selective death of lower motor neurons, including those innervating the limbs, intercostal muscles, and diaphragm, is predominantly responsible for this fatal phenotype. Neural expression of a membralin transgene completely rescues membralin mutant mice. Mechanistically, we show that membralin interacts with Erlin2, an endoplasmic reticulum (ER) membrane protein that is located in lipid rafts and known to be important in ER-associated protein degradation (ERAD). Accordingly, the degradation rate of ERAD substrates is attenuated in cells lacking membralin. Membralin mutations or deficiency in mouse models induces ER stress, rendering neurons more vulnerable to cell death. Our study reveals a critical role of membralin in motor neuron survival and suggests a novel mechanism for early-onset motor neuron disease.

Feasibility of discriminating uric acid from non-uric acid renal stones using consecutive spatially registered low- and high-energy scans obtained on a conventional CT scanner.

OBJECTIVE: The objective of our study was to show the feasibility of distinguishing between uric acid (UA) and non-UA renal stones using two consecutive spatially registered low- and high-energy scans acquired on a conventional CT system. SUBJECTS AND METHODS: A total of 33 patients undergoing clinically indicated dual-source dual-energy CT examinations to differentiate UA from non-UA renal stones were enrolled in this study. Immediately after patients underwent clinically indicated dual-source dual-energy CT, two consecutive scans (one at 80 kV and one at 140 kV) were obtained on a conventional CT scanner over the region limited to the stones identified on the dual-source scans. After 3D deformable registration of the 80- and 140-kV images, UA and non-UA stones were identified using commercial software. The sensitivity, specificity, and accuracy of stone classification were calculated using the dual-source results as the reference standard. RESULTS: A total of 469 stones were identified in the dual-source examinations (26 UA and 443 non-UA stones). The average in-plane stone diameter was 4.4 ± 2.5 (SD) mm (range, 2.0-18.9 mm). The overall sensitivity, specificity, and accuracy for identifying UA stones were 73.1%, 90.1%, and 89.1%, respectively. The sensitivity, specificity, and accuracy were 94.7%, 96.9%, and 96.8% for stones 3 mm or larger (n = 341 [19 UA and 322 non-UA]). CONCLUSION: Accurate differentiation of UA from non-UA renal stones is feasible using two consecutively acquired and spatially registered conventional CT scans.

Use of dual-energy CT and virtual non-calcium techniques to evaluate post-traumatic bone bruises in knees in the subacute setting.

OBJECTIVE: The purpose of this study was to determine the ability of dual-energy computed tomography (DECT) and virtual non-calcium (VNCa) imaging to detect magnetic resonance imaging (MRI)-demonstrated bone bruises several weeks after unilateral knee injury. MATERIALS AND METHODS: Patients with unilateral knee injury and MRI-confirmed bone bruises who had undergone a DECT scan of both knees were retrospectively identified. Two radiologists evaluated VNCa images for bruises in four regions per knee without knowing the MRI results. The mean CT numbers were calculated for the lesion-positive and lesion-negative regions of the injured knee, and the contralateral knee. RESULTS: Fourteen patients with a total of 36 regions positive for bone bruises on MRI were identified. The median delay between injury and DECT was 37 days (range, 11-99 days). The mean CT numbers in VNCa images for lesion-positive and lesion-negative regions were -7.6 ± 24.9 HU and -58.2 ± 19.5 HU, respectively. There were no significant differences in mean CT number between the lesion-negative regions in the injured knee and the contralateral knee. No resolution of bruising was seen before week 5, and bone bruising was still identifiable in one out of the two patients scanned at 10 weeks following injury. CONCLUSIONS: DECT and VNCa images can identify bone bruising for at least 10 weeks after injury.

Reducing image noise in computed tomography (CT) colonography: effect of an integrated circuit CT detector.

OBJECTIVE: To investigate whether the integrated circuit (IC) detector results in reduced noise in computed tomography (CT) colonography (CTC). METHODS: Three hundred sixty-six consecutive patients underwent clinically indicated CTC using the same CT scanner system, except for a difference in CT detectors (IC or conventional). Image noise, patient size, and scanner radiation output (volume CT dose index) were quantitatively compared between patient cohorts using each detector system, with separate comparisons for the abdomen and pelvis. RESULTS: For the abdomen and pelvis, despite significantly larger patient sizes in the IC detector cohort (both P < 0.001), image noise was significantly lower (both P < 0.001), whereas volume CT dose index was unchanged (both P > 0.18). Based on the observed image noise reduction, radiation dose could alternatively be reduced by approximately 20% to result in similar levels of image noise. CONCLUSION: Computed tomography colonography images acquired using the IC detector had significantly lower noise than images acquired using the conventional detector. This noise reduction can permit further radiation dose reduction in CTC.

Differentiating calcium oxalate and hydroxyapatite stones in vivo using dual-energy CT and urine supersaturation and pH values.

RATIONALE AND OBJECTIVES: Knowledge of urinary stone composition can guide therapeutic intervention for patients with calcium oxalate (CaOx) or hydroxyapatite (HA) stones. In this study, we determined the accuracy of noninvasive differentiation of these two stone types using dual-energy CT (DECT) and urine supersaturation (SS) and pH values. MATERIALS AND METHODS: Patients who underwent clinically indicated DECT scanning for stone disease and subsequent surgical intervention were enrolled. Stone composition was determined using infrared spectroscopy. DECT images were processed using custom-developed software that evaluated the ratio of CT numbers between low- and high-energy images. Clinical information, including patient age, gender, and urine pH and supersaturation profile, was obtained from electronic medical records. Simple and multiple logistic regressions were used to determine if the ratio of CT numbers could discriminate CaOx from HA stones alone or in conjunction with urine supersaturation and pH. RESULTS: Urinary stones (CaOx n = 43, HA n = 18) from 61 patients were included in this study. In a univariate model, DECT data, urine SS-HA, and urine pH had an area under the receiver operating characteristic curve of 0.78 (95% confidence interval [CI] 0.66-0.91, P = .016), 0.76 (95% CI 0.61-0.91, P = .003), and 0.60 (95% CI 0.44-0.75, P = .20), respectively, for predicting stone composition. The combination of CT data and the urinary SS-HA had an area under the receiver operating characteristic curve of 0.79 (95% CI 0.66-0.92, P = .007) for correctly differentiating these two stone types. CONCLUSIONS: DECT differentiated between CaOx and HA stones similarly to SS-HA, whereas pH was a poor discriminator. The combination of DECT and urine SS or pH data did not improve this performance.

A Pd(II)-catalyzed asymmetric approach toward chiral [3.3.1]-bicyclic ketals using 2-hydroxyphenylboronic acid as a pro-bis(nucleophile).

Enantioselective Pd(II)-catalyzed construction of [3.3.1]-bicyclic ketals from 2-hydroxyphenylboronic acid and enone is reported, yielding enantioenriched [3.3.1]-bicyclic ketals in up to 97% yields and 98% ee.

Urinary stone differentiation in patients with large body size using dual-energy dual-source computed tomography.

OBJECTIVE: To evaluate the ability of 100/Sn140 kV (Sn, tin filter) dual-energy computed tomography (CT) to differentiate urinary stone types in a patient cohort with a wide range of body sizes. METHODS: Eighty human urinary stones were categorised into four groups (uric acid; cystine; struvite, oxalate and brushite together; and apatite) and imaged in 30-50-cm-wide water tanks using clinical 100/Sn140 kV protocols. The CT number ratio (CTR) between the low- and high-energy images was calculated. Thresholds for differentiating between stone groups were determined using receiver operating characteristics (ROC) analysis. Additionally, 86 stones from 66 patients were characterised using the size-adaptive CTR thresholds determined in the phantom study. RESULTS: In phantoms, the area under the ROC curve for differentiating between stone groups ranged from 0.71 to 1.00, depending on phantom size. In patients, body width ranged from 28.5 to 50.0 cm, and 79.1 % of stones were correctly characterised. Sensitivity and specificity for correctly identifying the stone category were 100 % and 100 % (group 1), 100 % and 95.3 % (group 2), 85.7 % and 60.9 % (group 3), and 52.6 % and 92.5 % (group 4). CONCLUSION: Dual-energy CT can provide in vivo urinary stone characterisation for patients over a wide range of body sizes. KEY POINTS: • Dual-energy CT helps assessment of urinary stone composition in vivo. • 100/Sn140 kV DECT differentiates among four stone types with 79.1 % accuracy. • In vivo diagnostic test achievable in patients with many body sizes.

Differentiation of calcium oxalate monohydrate and calcium oxalate dihydrate stones using quantitative morphological information from micro-computerized and clinical computerized tomography.

PURPOSE: We differentiated calcium oxalate monohydrate and calcium oxalate dihydrate kidney stones using micro and clinical computerized tomography images. MATERIALS AND METHODS: A total of 22 calcium oxalate monohydrate and 15 calcium oxalate dihydrate human kidney stones were scanned using a commercial micro-computerized tomography scanner with a pixel size of 7 to 23 µm. Under an institutional review board approved protocol, image data on 10 calcium oxalate monohydrate and 9 calcium oxalate dihydrate stones greater than 5 mm were retrieved from a total of 80 patients who underwent clinical dual energy computerized tomography for clinical indications and had stones available for infrared spectroscopic compositional analysis. Micro and clinical computerized tomography images were processed using in-house software, which quantified stone surface morphology with curvature based calculations. A shape index was generated as a quantitative shape metric to differentiate calcium oxalate monohydrate from calcium oxalate dihydrate stones. Statistical tests were used to test the performance of the shape index. RESULTS: On micro-computerized tomography images the shape index of calcium oxalate monohydrate and calcium oxalate dihydrate stones significantly differed (ROC curve AUC 0.92, p <0.0001). At the optimal cutoff sensitivity was 0.93 and specificity was 0.91. On clinical computerized tomography images a significant morphological difference was also detected (p = 0.007). AUC, sensitivity and specificity were 0.90, 1 and 0.73, respectively. CONCLUSIONS: On micro and clinical computerized tomography images a morphological difference was detectable in calcium oxalate monohydrate and calcium oxalate dihydrate stones larger than 5 mm. The shape index is a highly promising method that can distinguish calcium oxalate monohydrate and calcium oxalate dihydrate stones with reasonable accuracy.

Synthesis of axially chiral oxazoline-carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe(2).

Axially chiral oxazoline-carbene ligands with an N-naphthyl framework were successfully prepared, and their coordination behavior with AuCl·SMe(2) was also investigated, affording the corresponding Au(I) complexes in moderate to high yields.

Toward biphasic computed tomography (CT) enteric contrast: material classification of luminal bismuth and mural iodine in a small-bowel phantom using dual-energy CT.

OBJECTIVE: To develop dual-energy computed tomography methods for identification of hyperenhancing, hypoenhancing, and nonenhancing small-bowel pathologies. METHODS: Small-bowel phantoms simulating varying patient sizes and polyp types (hyperenhancing, hypoenhancing, and nonenhancing) contained bismuth suspension in the lumen. Dual-energy CT was performed at 80/140 kV and 100/140 kV. Computed tomographic number ratios (CT numbers at low/high kilovoltage) were calculated. Two radiologists evaluated polyp detection and conspicuity using bismuth-only, iodine-only, iodine-overlay, and mixed-kilovoltage displays. RESULTS: Computed tomographic ratios for bismuth and iodine did not overlap. For hyperenhancing and nonenhancing polyps at 80/140 kV, iodine-overlay display yielded higher detection rate (96%, 94%) and conspicuity score (3.5, 3.1) than mixed-kilovoltage images (88%, 68%; 1.5, 2.7). Mixed-kV images performed slightly better for hypoenhancing polyps (92%, 3.4 vs. <80%, <2.9). Similar results were observed at 100/140kV. CONCLUSIONS: Dual-energy CT and a bismuth-containing enteric contrast permitted simultaneous identification of hyperenhancing, hypoenhancing, and nonenhancing polyps over a range of patient sizes.

Characterisation of urinary stones in the presence of iodinated contrast medium using dual-energy CT: a phantom study.

OBJECTIVE: To develop a dual-energy CT (DECT) method for differentiating uric acid (UA) from non-UA stones in the presence of iodinated contrast medium. METHODS: Thirty UA and 45 non-UA stones were selected after infra-red spectroscopic analysis and independently placed in a 1.5-ml vial, which was filled first with saline and then with increasing concentrations of iodine. For each condition, tubes were put in a 35-cm water phantom and examined using a dual-source CT system at 100 and 140 kV. Virtual unenhanced images created from CT data sets of the stones in iodine-containing solutions provided position and volume information. This map was used to calculate a CT number ratio to differentiate stone type. A region-growing method was developed to improve the ability to differentiate between UA and non-UA stones with iodinated contrast medium. RESULTS: The sensitivity for detecting UA stones was 100 % for unenhanced images but fell to 18 % with 20 mgI/ml iodine solution and 0 % for higher concentrations. With region growing, the sensitivity for detecting UA stones was increased to 100 %, 82 %, 57 %, 50 % and 21 % for iodine solutions of 20, 40, 60, 80 and 100 mgI/ml. CONCLUSION: The region-growing method improves differentiation of UA from non-UA stones on contrast-enhanced DECT urograms. KEY POINTS: Computed tomography is widely used to assess renal tract calculi. Dual-energy CT can assess stone composition and provide virtual unenhanced images. However, iodinated contrast medium affects the volume estimation for urinary stones. CTR of stones is altered by the surrounding iodine in CT urograms. The region-growing method improves the identification of uric acid stones.

Ph2PI as a reduction/phosphination reagent: providing easy access to phosphine oxides.

The reaction of aldehydes with Ph(2)PI provides a facile way to the synthesis of pentavalent phosphine compounds with moderate to good yields.

Kidney stone volume estimation from computerized tomography images using a model based method of correcting for the point spread function.

PURPOSE: We propose a method to improve the accuracy of volume estimation of kidney stones from computerized tomography images. MATERIALS AND METHODS: The proposed method consisted of 2 steps. A threshold equal to the average of the computerized tomography number of the object and the background was first applied to determine full width at half maximum volume. Correction factors were then applied, which were precalculated based on a model of a sphere and a 3-dimensional gaussian point spread function. The point spread function was measured in a computerized tomography scanner to represent the response of the scanner to a point-like object. Method accuracy was validated using 6 small cylindrical phantoms with 2 volumes of 21.87 and 99.9 mm(3), and 3 attenuations, respectively, and 76 kidney stones with a volume range of 6.3 to 317.4 mm(3). Volumes estimated by the proposed method were compared with full width at half maximum volumes. RESULTS: The proposed method was significantly more accurate than full width at half maximum volume (p <0.0001). The magnitude of improvement depended on stone volume with smaller stones benefiting more from the method. For kidney stones 10 to 20 mm(3) in volume the average improvement in accuracy was the greatest at 19.6%. CONCLUSIONS: The proposed method achieved significantly improved accuracy compared with threshold methods. This may lead to more accurate stone management.

Me3SiI-promoted reaction of salicylic aldehydes with ketones: a facile way to construct benzopyranic [2,3-b]ketals and spiroketals.

Me(3)SiI-promoted reaction of salicylic aldehydes with ketones via arylmethylation at the α-site of the carbonyl group and cyclodehydration of keto-diol provided a facile way to construct heteroannular ketals, furnishing benzopyranic [2,3-b]ketals and spiroketals in moderate to good yields.

An unusual Me3SiI-promoted [4+2] annulation and reduction: an efficient approach to construct 4H-benzopyrans.

Me(3)SiI-promoted reaction of salicylic aldehydes with ß-dicarbonyl compounds provided a facile way to construct 4H-benzopyrans in moderate to good yields. This tandem reaction proceeds with high efficiency through nucleophilic addition, silyl enol ether formation, substitution, reduction, and intramolecular nucleophilic cyclization.

A highly efficient kinetic resolution of Morita-Baylis-Hillman adducts achieved by N-Ar axially chiral Pd-complexes catalyzed asymmetric allylation.

Palladium complexes with an axially chiral N-Ar framework have been developed. These complexes showed high stereoselectivities in asymmetric allylic arylation to achieve the kinetic resolution of Morita-Baylis-Hillman adducts, affording up to 99% ee of (E)-allylation products and 92% ee of recovered Morita-Baylis-Hillman adducts.

Dynamic CT technique for assessment of wrist joint instabilities.

PURPOSE: To develop a 4D [three-dimensional (3D) + time] CT technique to capture high spatial and temporal resolution images of wrist joint motion so that dynamic joint instabilities can be detected before the development of static joint instability and onset of osteoarthritis (OA). METHODS: A cadaveric wrist was mounted onto a custom motion simulator and scanned with a dual source CT scanner during radial-ulnar deviation. A dynamic 4D CT technique was utilized to reconstruct images at 20 equidistant time points from one motion cycle. 3D images of carpal bones were generated using volume rendering techniques (VRT) at each of the 20 time points and then 4D movies were generated to depict the dynamic joint motion. The same cadaveric wrist was also scanned after cutting all portions of the scapholunate interosseus ligament to simulate scapholunate joint instability. Image quality were assessed on an ordinal scale (1-4, 4 being excellent) by three experienced orthopedic surgeons (specialized in hand surgery) by scoring 2D axial images. Dynamic instability was evaluated by the same surgeons by comparing the two 4D movies of joint motion. Finally, dose reduction was investigated using the cadaveric wrist by scanning at different dose levels to determine the lowest radiation dose that did not substantially alter diagnostic image quality. RESULTS: The mean image quality scores for dynamic and static CT images were 3.7 and 4.0, respectively. The carpal bones, distal radius and ulna, and joint spaces were clearly delineated in the 3D VRT images, without motion blurring or banding artifacts, at all time points during the motion cycle. Appropriate viewing angles could be interactively selected to view any articulating structure using different 3D processing techniques. The motion of each carpal bone and the relative motion among the carpal bones were easily observed in the 4D movies. Joint instability was correctly and easily detected in the scan performed after the ligament was cut by observing the relative motion between the scaphoid and lunate bones. Diagnostic capability was not sacrificed with a volume CT dose index (CTDI(vol)) as low as 18 mGy for the whole scan, with estimated skin dose of approximately 33 mGy, which is much lower than the threshold for transient skin erythema (2000 mGy). CONCLUSIONS: The proposed dynamic 4D CT imaging technique generated high spatial and high temporal resolution images without requiring periodic joint motion. Preliminary results from this cadaveric study demonstrate the feasibility of detecting joint instability using this technique.

Dual-energy dual-source CT with additional spectral filtration can improve the differentiation of non-uric acid renal stones: an ex vivo phantom study.

OBJECTIVE: The purpose of this study was to determine the ex vivo ability of dual-energy dual-source CT (DSCT) with additional tin filtration to differentiate among five groups of human renal stone types. MATERIALS AND METHODS: Forty-three renal stones of 10 types were categorized into five primary groups on the basis of effective atomic numbers, which were calculated as the weighted average of the atomic numbers of constituent atoms. Stones were embedded in porcine kidneys and placed in a 35-cm water phantom. Dual-energy DSCT scans were performed at 80 and 140 kV with and without tin filtration of the 140-kV beam. The CT number ratio, defined as the ratio of the CT number of a given material in the low-energy image to the CT number of the same material in the high-energy image, was calculated on a volumetric voxel-by-voxel basis for each stone. Statistical analysis was performed, and receiver operating characteristic (ROC) curves were plotted to compare the difference in CT number ratio with and without tin filtration, and to measure the discrimination among stone groups. RESULTS: The CT number ratio of non-uric acid stones increased on average by 0.17 (range, 0.03-0.36) with tin filtration. The CT number ratios for non-uric acid stone groups were not significantly different (p > 0.05) between any of the two adjacent groups without tin filtration. Use of the additional tin filtration on the high-energy x-ray tube significantly improved the separation of non-uric acid stone types by CT number ratio (p < 0.05). The area under the ROC curve increased from 0.78 to 0.84 without fin filtration and to 0.89-0.95 with tin filtration. CONCLUSION: Our results showed better separation among different stone types when additional tin filtration was used on dual-energy DSCT. The increased spectral separation allowed a five-group stone classification scheme. Some overlapping between particular stone types still exists, including brushite and calcium oxalate.