Effectiveness of Medical Cannabis for the Treatment of Depression: A Naturalistic Outpatient Study.

BACKGROUND: There is a lack of studies on the course and effectiveness of medical cannabis in the treatment of major depressive disorder (MDD). METHODS: Retrospective longitudinal (18 weeks) study of n=59 outpatients with MDD, treated with medical cannabis via a telemedical platform. Previous treatment with antidepressant medication was required for inclusion into the study. Standardized data collection was carried out at entry and during monthly consultations. Severity of depression was measured on a 0-10 point rating scale. Side-effects were assessed by a checklist. RESULTS: Patients were 20-54 years old; 72.9% were male; one third reported times of regular cannabis consumption within the previous five years. Drop-out rate was 22% after 18 weeks. Mean severity of depression decreased from 6.9 points (SD 1.5) at entry to 3.8 points (2.7) at week 18 (baseline observation carried forward; 95% CI for the mean difference: 2.4 to 3.8; p<0.001). A treatment response (>50% reduction of the initial score) was seen in 50.8% at week 18. One third of patients complained about side effects, none was considered as severe. Concomitant antidepressant medication (31% of patients) was not associated with outcome. CONCLUSIONS: Medical cannabis was well tolerated and dropout rate was comparable to those in clinical trials of antidepressant medication. Patients reported a clinically significant reduction of depression severity. Further research on the effectiveness of medical cannabis for MDD seems warranted. Risks of this medication, such as sustaining or inducing a cannabis use disorder, or side effects such as poor concentration, must be taken into consideration.

Characterizing and utilizing oxygen-dependent promoters for efficient dynamic metabolic engineering.

Promoters adjust cellular gene expression in response to internal or external signals and are key elements for implementing dynamic metabolic engineering concepts in fermentation processes. One useful signal is the dissolved oxygen content of the culture medium, since production phases often proceed in anaerobic conditions. Although several oxygen-dependent promoters have been described, a comprehensive and comparative study is missing. The goal of this work is to systematically test and characterize 15 promoter candidates that have been previously reported to be induced upon oxygen depletion in Escherichia coli. For this purpose, we developed a microtiter plate-level screening using an algal oxygen-independent flavin-based fluorescent protein and additionally employed flow cytometry analysis for verification. Various expression levels and dynamic ranges could be observed, and six promoters (nar-strong, nar-medium, nar-weak, nirB-m, yfiD-m, and fnrF8) appear particularly suited for dynamic metabolic engineering applications. We demonstrate applicability of these candidates for dynamic induction of enforced ATP wasting, a metabolic engineering approach to increase productivity of microbial strains that requires a narrow level of ATPase expression for optimal function. The selected candidates exhibited sufficient tightness under aerobic conditions while, under complete anaerobiosis, driving expression of the cytosolic F1-subunit of the ATPase from E. coli to levels that resulted in unprecedented specific glucose uptake rates. We finally utilized the nirB-m promoter to demonstrate the optimization of a two-stage lactate production process by dynamically enforcing ATP wasting, which is automatically turned on in the anaerobic (growth-arrested) production phase to boost the volumetric productivity. Our results are valuable for implementing metabolic control and bioprocess design concepts that use oxygen as signal for regulation and induction.

Comprehensive comparison of dual-energy computed tomography and magnetic resonance imaging for the assessment of bone marrow edema and fracture lines in acute vertebral fractures.

OBJECTIVES: To compare dual-energy CT (DECT) and MRI for assessing presence and extent of traumatic bone marrow edema (BME) and fracture line depiction in acute vertebral fractures. METHODS: Eighty-eight consecutive patients who underwent dual-source DECT and 3-T MRI of the spine were retrospectively analyzed. Five radiologists assessed all vertebrae for presence and extent of BME and for identification of acute fracture lines on MRI and, after 12 weeks, on DECT series. Additionally, image quality, image noise, and diagnostic confidence for overall diagnosis of acute vertebral fracture were assessed. Quantitative analysis of CT numbers was performed by a sixth radiologist. Two radiologists analyzed MRI and grayscale DECT series to define the reference standard. RESULTS: For assessing BME presence and extent, DECT showed high sensitivity (89% and 84%, respectively) and specificity (98% in both), and similarly high diagnostic confidence compared to MRI (2.30 vs. 2.32; range 0-3) for the detection of BME (p = .72). For evaluating acute fracture lines, MRI achieved high specificity (95%), moderate sensitivity (76%), and a significantly lower diagnostic confidence compared to DECT (2.42 vs. 2.62, range 0-3) (p < .001). A cutoff value of - 0.43 HU provided a sensitivity of 89% and a specificity of 90% for diagnosing BME, with an overall AUC of 0.96. CONCLUSIONS: DECT and MRI provide high diagnostic confidence and image quality for assessing acute vertebral fractures. While DECT achieved high overall diagnostic accuracy in the analysis of BME presence and extent, MRI provided moderate sensitivity and lower confidence for evaluating fracture lines. KEY POINTS: • In the setting of spinal trauma, dual-energy CT (DECT) is highly accurate in the evaluation of acute vertebral fractures and bone marrow edema presence and extent. • MRI provides moderate sensitivity and lower diagnostic confidence for the depiction of acute fracture lines, when compared to DECT, which might result in potentially inaccurate and underestimated severity assessment of injuries in certain cases when no fracture lines are visible on MRI. • DECT may represent a valid imaging alternative to MRI in specific settings of acute spinal trauma and in follow-up examinations, especially in elderly or unstable patients and in cases of subtle or complex orientated fracture lines.

Diagnostic accuracy of quantitative dual-energy CT-based volumetric bone mineral density assessment for the prediction of osteoporosis-associated fractures.

OBJECTIVES: To evaluate the predictive value of volumetric bone mineral density (BMD) assessment of the lumbar spine derived from phantomless dual-energy CT (DECT)-based volumetric material decomposition as an indicator for the 2-year occurrence risk of osteoporosis-associated fractures. METHODS: L1 of 92 patients (46 men, 46 women; mean age, 64 years, range, 19-103 years) who had undergone third-generation dual-source DECT between 01/2016 and 12/2018 was retrospectively analyzed. For phantomless BMD assessment, dedicated DECT postprocessing software using material decomposition was applied. Digital files of all patients were sighted for 2 years following DECT to obtain the incidence of osteoporotic fractures. Receiver operating characteristic (ROC) analysis was used to calculate cut-off values and logistic regression models were used to determine associations of BMD, sex, and age with the occurrence of osteoporotic fractures. RESULTS: A DECT-derived BMD cut-off of 93.70 mg/cm3 yielded 85.45% sensitivity and 89.19% specificity for the prediction to sustain one or more osteoporosis-associated fractures within 2 years after BMD measurement. DECT-derived BMD was significantly associated with the occurrence of new fractures (odds ratio of 0.8710, 95% CI, 0.091-0.9375, p < .001), indicating a protective effect of increased DECT-derived BMD values. Overall AUC was 0.9373 (CI, 0.867-0.977, p < .001) for the differentiation of patients who sustained osteoporosis-associated fractures within 2 years of BMD assessment. CONCLUSIONS: Retrospective DECT-based volumetric BMD assessment can accurately predict the 2-year risk to sustain an osteoporosis-associated fracture in at-risk patients without requiring a calibration phantom. Lower DECT-based BMD values are strongly associated with an increased risk to sustain fragility fractures. KEY POINTS: •Dual-energy CT-derived assessment of bone mineral density can identify patients at risk to sustain osteoporosis-associated fractures with a sensitivity of 85.45% and a specificity of 89.19%. •The DECT-derived BMD threshold for identification of at-risk patients lies above the American College of Radiology (ACR) QCT guidelines for the identification of osteoporosis (93.70 mg/cm3 vs 80 mg/cm3).

Diagnostic accuracy of color-coded virtual noncalcium reconstructions derived from portal venous phase dual-energy CT in the assessment of lumbar disk herniation.

OBJECTIVES: To investigate the diagnostic accuracy of color-coded contrast-enhanced dual-energy CT virtual noncalcium (VNCa) reconstructions for the assessment of lumbar disk herniation compared to unenhanced VNCa imaging. METHODS: A total of 91 patients were retrospectively evaluated (65 years ± 16; 43 women) who had undergone third-generation dual-source dual-energy CT and 3.0-T MRI within an examination interval up to 3 weeks between November 2019 and December 2020. Eight weeks after assessing unenhanced color-coded VNCa reconstructions for the presence and degree of lumbar disk herniation, corresponding contrast-enhanced portal venous phase color-coded VNCa reconstructions were independently analyzed by the same five radiologists. MRI series were additionally analyzed by one highly experienced musculoskeletal radiologist and served as reference standard. RESULTS: MRI depicted 210 herniated lumbar disks in 91 patients. VNCa reconstructions derived from contrast-enhanced CT scans showed similar high overall sensitivity (93% vs 95%), specificity (94% vs 95%), and accuracy (94% vs 95%) for the assessment of lumbar disk herniation compared to unenhanced VNCa images (all p > .05). Interrater agreement in VNCa imaging was excellent for both, unenhanced and contrast-enhanced CT (κ = 0.84 vs κ = 0.86; p > .05). Moreover, ratings for diagnostic confidence, image quality, and noise differed not significantly between unenhanced and contrast-enhanced VNCa series (all p > .05). CONCLUSIONS: Color-coded VNCa reconstructions derived from contrast-enhanced dual-energy CT yield similar diagnostic accuracy for the depiction of lumbar disk herniation compared to unenhanced VNCa imaging and therefore may improve opportunistic retrospective lumbar disk herniation assessment, particularly in case of staging CT examinations. KEY POINTS: • Color-coded dual-source dual-energy CT virtual noncalcium (VNCa) reconstructions derived from portal venous phase yield similar high diagnostic accuracy for the assessment of lumbar disk herniation compared to unenhanced VNCa CT series (94% vs 95%) with MRI serving as a standard of reference. • Diagnostic confidence, image quality, and noise levels differ not significantly between unenhanced and contrast-enhanced portal venous phase VNCa dual-energy CT series. • Dual-source dual-energy CT might have the potential to improve opportunistic retrospective lumbar disk herniation assessment in CT examinations performed for other indications through reconstruction of VNCa images.

Farnesyl pyrophosphate compartmentalization in the green microalga Chlamydomonas reinhardtii during heterologous (E)-α-bisabolene production.

BACKGROUND: Eukaryotic algae have recently emerged as hosts for metabolic engineering efforts to generate heterologous isoprenoids. Isoprenoid metabolic architectures, flux, subcellular localization, and transport dynamics have not yet been fully elucidated in algal hosts. RESULTS: In this study, we investigated the accessibility of different isoprenoid precursor pools for C15 sesquiterpenoid generation in the cytoplasm and chloroplast of Chlamydomonas reinhardtii using the Abies grandis bisabolene synthase (AgBS) as a reporter. The abundance of the C15 sesquiterpene precursor farnesyl pyrophosphate (FPP) was not increased in the cytosol by co-expression and fusion of AgBS with different FPP synthases (FPPSs), indicating limited C5 precursor availability in the cytoplasm. However, FPP was shown to be available in the plastid stroma, where bisabolene titers could be improved several-fold by FPPSs. Sesquiterpene production was greatest when AgBS-FPPS fusions were directed to the plastid and could further be improved by increasing the gene dosage. During scale-up cultivation with different carbon sources and light regimes, specific sesquiterpene productivities from the plastid were highest with CO2 as the only carbon source and light:dark illumination cycles. Potential prenyl unit transporters are proposed based on bioinformatic analyses, which may be in part responsible for our observations. CONCLUSIONS: Our findings indicate that the algal chloroplast can be harnessed in addition to the cytosol to exploit the full potential of algae as green cell factories for non-native sesquiterpenoid generation. Identification of a prenyl transporter may be leveraged for further extending this capacity.

Development and evaluation of a computer-based decision support system for diffuse lung diseases at high-resolution computed tomography.

BACKGROUND: High-resolution computed tomography (HRCT) is essential in narrowing the possible differential diagnoses of diffuse and interstitial lung diseases. PURPOSE: To investigate the value of a novel computer-based decision support system (CDSS) for facilitating diagnosis of diffuse lung diseases at HRCT. MATERIAL AND METHODS: A CDSS was developed that includes about 100 different illustrations of the most common HRCT signs and patterns and describes the corresponding pathologies in detail. The logical set-up of the software facilitates a structured evaluation. By selecting one or more CT patterns, the program generates a ranked list of the most likely differential diagnoses. Three independent and blinded radiology residents initially evaluated 40 cases with different lung diseases alone; after at least 12 weeks, observers re-evaluated all cases using the CDSS. RESULTS: In 40 patients, a total of 113 HRCT patterns were evaluated. The percentage of correctly classified patterns was higher with CDSS (96.8%) compared to assessment without CDSS (90.3%; P < 0.01). Moreover, the percentage of correct diagnosis (81.7% vs. 64.2%) and differential diagnoses (89.2% vs. 38.3%) were superior with CDSS compared to evaluation without CDSS (both P < 0.01). CONCLUSION: Addition of a CDSS using a structured approach providing explanations of typical HRCT patterns and graphical illustrations significantly improved the performance of trainees in characterizing and correctly identifying diffuse lung diseases.

Incremental diagnostic value of color-coded virtual non-calcium dual-energy CT for the assessment of traumatic bone marrow edema of the scaphoid.

OBJECTIVES: To investigate the diagnostic accuracy of color-coded dual-energy CT virtual non-calcium (VNCa) reconstructions for the assessment of bone marrow edema (BME) of the scaphoid in patients with acute wrist trauma. METHODS: Our retrospective study included data from 141 patients (67 women, 74 men; mean age 43 years, range 19-80 years) with acute wrist trauma who had undergone third-generation dual-source dual-energy CT and 3-T MRI within 7 days. Eight weeks after assessment of conventional grayscale dual-energy CT scans for the presence of fractures, corresponding color-coded VNCa reconstructions were independently analyzed by the same six radiologists for the presence of BME. CT numbers on VNCa reconstructions were evaluated by a seventh radiologist. Consensus reading of MRI series by two additional radiologists served as the reference standard. RESULTS: MRI depicted 103 scaphoideal zones with BME in 76 patients. On qualitative analysis, VNCa images yielded high overall sensitivity (580/618 [94%]), specificity (1880/1920 [98%]), and accuracy (2460/2538 [97%]) for assessing BME as compared with MRI as reference standard. The interobserver agreement was excellent (κ = 0.98). CT numbers derived from VNCa images were significantly different in zones with and without edema (p < 0.001). A cutoff value of - 46 Hounsfield units provided a sensitivity of 91% and specificity of 97% for differentiating edematous scaphoid lesions. Receiver operating characteristic curve analysis revealed an overall area under the curve of 0.98. CONCLUSIONS: Qualitative and quantitative analyses showed excellent diagnostic accuracy of color-coded VNCa reconstructions for assessing traumatic BME of the scaphoid compared to MRI. KEY POINTS: • Color-coded virtual non-calcium (VNCa) reconstructions yield excellent diagnostic accuracy in assessing bone marrow edema of the scaphoid. • VNCa imaging enables detection of non-displaced fractures that are occult on standard grayscale CT. • Diagnostic confidence is comparable between VNCa imaging and MRI.

Assessment of thoracic disk herniation by using virtual noncalcium dual-energy CT in comparison with standard grayscale CT.

OBJECTIVES: To determine the diagnostic accuracy of dual-energy CT (DECT) virtual noncalcium (VNCa) reconstructions for assessing thoracic disk herniation compared to standard grayscale CT. METHODS: In this retrospective study, 87 patients (1131 intervertebral disks; mean age, 66 years; 47 women) who underwent third-generation dual-source DECT and 3.0-T MRI within 3 weeks between November 2016 and April 2020 were included. Five blinded radiologists analyzed standard DECT and color-coded VNCa images after a time interval of 8 weeks for the presence and degree of thoracic disk herniation and spinal nerve root impingement. Consensus reading of independently evaluated MRI series served as the reference standard, assessed by two separate experienced readers. Additionally, image ratings were carried out by using 5-point Likert scales. RESULTS: MRI revealed a total of 133 herniated thoracic disks. Color-coded VNCa images yielded higher overall sensitivity (624/665 [94%; 95% CI, 0.89-0.96] vs 485/665 [73%; 95% CI, 0.67-0.80]), specificity (4775/4990 [96%; 95% CI, 0.90-0.98] vs 4066/4990 [82%; 95% CI, 0.79-0.84]), and accuracy (5399/5655 [96%; 95% CI, 0.93-0.98] vs 4551/5655 [81%; 95% CI, 0.74-0.86]) for the assessment of thoracic disk herniation compared to standard CT (all p < .001). Interrater agreement was excellent for VNCa and fair for standard CT (ϰ = 0.82 vs 0.37; p < .001). In addition, VNCa imaging achieved higher scores regarding diagnostic confidence, image quality, and noise compared to standard CT (all p < .001). CONCLUSIONS: Color-coded VNCa imaging yielded substantially higher diagnostic accuracy and confidence for assessing thoracic disk herniation compared to standard CT. KEY POINTS: • Color-coded VNCa reconstructions derived from third-generation dual-source dual-energy CT yielded significantly higher diagnostic accuracy for the assessment of thoracic disk herniation and spinal nerve root impingement compared to standard grayscale CT. • VNCa imaging provided higher diagnostic confidence and image quality at lower noise levels compared to standard grayscale CT. • Color-coded VNCa images may potentially serve as a viable imaging alternative to MRI under circumstances where MRI is unavailable or contraindicated.

Color-coded virtual non-calcium dual-energy CT for the depiction of bone marrow edema in patients with acute knee trauma: a multireader diagnostic accuracy study.

OBJECTIVES: To evaluate the diagnostic accuracy of dual-energy computed tomography (CT) virtual non-calcium (VNCa) reconstructions for the depiction of traumatic knee bone marrow edema. METHODS: Fifty-seven patients (mean age, 50 years; range, 20-82 years) with acute knee trauma further divided into 30 women and 27 men, who had undergone third-generation dual-source dual-energy CT and 3-T magnetic resonance imaging (MRI) within 7 days between January 2017 and May 2018, were retrospectively analyzed. Six radiologists, blinded to clinical and MRI information, independently analyzed conventional grayscale dual-energy CT series for fractures; after 8 weeks, readers evaluated color-coded VNCa reconstructions for the presence of bone marrow edema in six femoral and six tibial regions. Quantitative analysis of CT numbers on VNCa reconstructions was performed by a seventh radiologist. Two additional radiologists, blinded to clinical and CT information, analyzed MRI series in consensus to define the reference standard. Sensitivity, specificity, and the area under the curve (AUC) were the primary metrics of diagnostic accuracy. RESULTS: MRI revealed 197 areas with bone marrow edema (91/342 femoral, 106/342 tibial). In the qualitative analysis, VNCa showed high overall sensitivity (1108/1182 [94%]) and specificity (2789/2922 [95%]) for depicting bone marrow edema. The AUC was 0.96 (femur) and 0.97 (tibia). A cutoff value of - 51 Hounsfield units (HU) provided high sensitivity (102/106 [96%]) and specificity (229/236 [97%]) for differentiating tibial bone marrow edema. CONCLUSIONS: In both quantitative and qualitative analyses, dual-energy CT VNCa reconstructions yielded excellent diagnostic accuracy for depicting traumatic knee bone marrow edema compared with MRI. KEY POINTS: • Dual-energy CT (DECT) virtual non-calcium (VNCa) reconstructions are highly accurate in depicting bone marrow edema of the femur and tibia. • Diagnostic confidence, image noise, and image quality were rated as equivalent in VNCa reconstructions and MRI (magnetic resonance imaging) series. • VNCa images may serve as an alternative imaging approach to MRI.

Intron-containing algal transgenes mediate efficient recombinant gene expression in the green microalga Chlamydomonas reinhardtii.

Among green freshwater microalgae, Chlamydomonas reinhardtii has the most comprehensive and developed molecular toolkit, however, advanced genetic and metabolic engineering driven from the nuclear genome is generally hindered by inherently low transgene expression levels. Progressive strain development and synthetic promoters have improved the capacity of transgene expression; however, the responsible regulatory mechanisms are still not fully understood. Here, we elucidate the sequence specific dynamics of native regulatory element insertion into nuclear transgenes. Systematic insertions of the first intron of the ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit 2 (rbcS2i1) throughout codon-optimized coding sequences (CDS) generates optimized algal transgenes which express reliably in C. reinhardtii. The optimal rbcS2i1 insertion site for efficient splicing was systematically determined and improved gene expression rates were shown using a codon-optimized sesquiterpene synthase CDS. Sequential insertions of rbcS2i1 were found to have a step-wise additive effect on all levels of transgene expression, which is likely correlated to a synergy of transcriptional machinery recruitment and mimicking the short average exon lengths natively found in the C. reinhardtii genome. We further demonstrate the value of this optimization with five representative transgene examples and provide guidelines for the design of any desired sequence with this strategy.

Virtual Noncalcium Dual-Energy CT: Detection of Lumbar Disk Herniation in Comparison with Standard Gray-scale CT.

Purpose To assess the diagnostic performance of dual-energy CT with reconstruction of virtual noncalcium (VNCa) images for the detection of lumbar disk herniation compared with standard CT image reconstruction. Materials and Methods For this retrospective study, 41 patients (243 intervertebral disks; overall mean age, 68 years; 24 women [mean age, 68 years] and 17 men [mean age, 68 years]) underwent clinically indicated third-generation, dual-source, dual-energy CT and 3.0-T MRI within 2 weeks between March 2017 and January 2018. Six radiologists, blinded to clinical and MRI information, independently evaluated conventional gray-scale dual-energy CT series for the presence and degree of lumbar disk herniation and spinal nerve root impingement. After 8 weeks, readers reevaluated examinations by using color-coded VNCa reconstructions. MRI evaluated by two separate experienced readers, blinded to clinical and dual-energy CT information, served as the standard of reference. Sensitivity and specificity were the primary metrics of diagnostic performance. Results A total of 112 herniated lumbar disks were depicted at MRI. VNCa showed higher overall sensitivity (612 of 672 [91%] vs 534 of 672 [80%]) and specificity (723 of 786 [92%] vs 665 of 786 [85%]) for detecting lumbar disk herniation compared with standard CT (all comparisons, P < .001). Interreader agreement was excellent for VNCa and substantial for standard CT (κ = 0.82 vs 0.67; P < .001). VNCa achieved superior diagnostic confidence, image quality, and noise scores compared with standard CT (all comparisons, P < .001). Conclusion Color-coded dual-energy CT virtual noncalcium reconstructions show substantially higher diagnostic performance and confidence for depicting lumbar disk herniation compared with standard CT. © RSNA, 2018.

Review of Clinical Applications for Virtual Monoenergetic Dual-Energy CT.

In this article, the authors discuss the technical background and summarize the current body of literature regarding virtual monoenergetic (VM) images derived from dual-energy CT data, which can be reconstructed between 40 and 200 keV. Substantially improved iodine attenuation at lower kiloelectron volt levels and reduced beam-hardening artifacts at higher kiloelectron volt levels have been demonstrated from all major manufacturers of dual-energy CT units. Improved contrast attenuation with VM imaging at lower kiloelectron volt levels enables better delineation and diagnostic accuracy in the detection of various vascular or oncologic abnormalities. Low-kiloelectron-volt VM imaging may be useful for salvaging CT studies with suboptimal contrast material delivery or providing additional information on the arterial vasculature obtained from venous phase acquisitions. For patients with renal impairment, substantial reductions in the use of iodinated contrast material can be achieved by using lower-energy VM imaging. The authors recommend routine reconstruction of VM images at 50 keV when using dual-energy CT to exploit the increased contrast properties. For reduction of beam-hardening artifacts, VM imaging at 120 keV is useful for the initial assessment.

Single- and dual-energy CT pulmonary angiography using second- and third-generation dual-source CT systems: comparison of radiation dose and image quality.

OBJECTIVES: To evaluate radiation exposure and image quality in matched patient cohorts for CT pulmonary angiography (CTPA) acquired in single- and dual-energy mode using second- and third-generation dual-source CT (DSCT) systems. METHODS: We retrospectively included 200 patients (mean age, 65.5 years ± 15.7 years) with suspected pulmonary embolism-equally divided into four study groups (n = 50) and matched by gender and body mass index. CTPA was performed with vendor-predefined second-generation (group A, 100-kV single-energy computed tomography (SECT); group B, 80/Sn140-kV dual-energy computed tomography (DECT)) or third-generation DSCT (group C, 100-kV SECT; group D, 90/Sn150-kV DECT) devices. Radiation metrics were assessed using a normalized scan range of 27.5 cm. For objective image quality evaluation, dose-independent figure-of-merit (FOM) contrast-to-noise ratios (CNRs) were calculated. Subjective image analysis included ratings for overall image quality, reader confidence, and image artifacts using five-point Likert scales. RESULTS: Calculations of the effective dose (ED) of radiation for a normalized scan range of 27.5 cm showed nonsignificant differences between SECT and DECT acquisitions for each scanner generation (p ≥ 0.253). The mean effective radiation dose was lower for third-generation groups C (1.5 mSv ± 0.8 mSv) and D (1.4 mSv ± 0.7 mSv) compared to second-generation groups A (2.5 mSv ± 0.9 mSv) and B (2.3 mSv ± 0.6 mSv) (both p ≤ 0.013). FOM-CNR measurements were highest for group D. Qualitative image parameters of overall image quality, reader confidence, and image artifacts showed nonsignificant differences among the four groups (p ≥ 0.162). CONCLUSIONS: Third-generation DSCT systems show lower radiation dose parameters for CTPA compared to second-generation DSCT. DECT can be performed with both scanner generations without radiation dose penalty or detrimental effects on image quality compared to SECT. KEY POINTS: • Radiation exposure showed nonsignificant differences between SECT and DECT for both DSCT scanner devices. • Dual-energy CTPA provides equivalent image quality compared to standard image acquisition. • Subjective image quality assessment was similar among the four study groups.

Dual-energy CT in early acute pancreatitis: improved detection using iodine quantification.

OBJECTIVES: To evaluate the diagnostic performance of a dual-energy computed tomography (DECT)-based technique using iodine quantification and fat fraction analysis for the diagnosis of early acute pancreatitis METHODS: In this retrospective study, 45 patients (35 men and 10 women; mean age, 54.9 ± 14.0 years) with early acute pancreatitis were included. Serum lipase levels and follow-up examinations served as the reference standard. A matched control group (n = 45) was assembled for evaluation of material decomposition values of normal pancreatic parenchyma. Three blinded radiologists independently interpreted all cases on conventional grayscale DECT series. In addition, readers re-evaluated all cases by manually performing region-of-interest (ROI) measurements on pancreatic-phase DECT material density images of the head, body, and tail of each patient's pancreas. Receiver operating characteristic (ROC) curve analysis was performed to estimate the optimal threshold for discriminating between inflammatory and normal pancreas parenchyma. RESULTS: DECT-based iodine density values showed significant differences between inflammatory (1.8 ± 0.3 mg/mL) and normal pancreatic parenchyma (2.7 ± 0.7 mg/mL) (p ≤ 0.01). Fat fraction measurements showed no significant differences (p = 0.08). The optimal iodine density threshold for the diagnosis of acute pancreatitis was 2.1 mg/mL with a sensitivity of 96% and specificity of 77%. Iodine quantification revealed an area under the curve (AUC) of 0.86, significantly higher compared to standard image evaluation of the radiologists (AUC, 0.80; sensitivity, 78%; specificity, 82%) (p < 0.01). CONCLUSION: DECT using iodine quantification allows for diagnosis of early acute pancreatitis with higher sensitivity compared to standard image evaluation. KEY POINTS: • Iodine density values showed significant differences between inflammatory and normal pancreatic parenchyma. • DECT using iodine quantification allows for diagnosis of early acute pancreatitis. • An iodine density of ≤ 2.1 mg/mL optimizes the diagnosis of acute pancreatitis.

Modified calcium subtraction in dual-energy CT angiography of the lower extremity runoff: impact on diagnostic accuracy for stenosis detection.

OBJECTIVES: To investigate the diagnostic accuracy of a modified three-material decomposition calcium subtraction (CS) algorithm for the detection of arterial stenosis in dual-energy CT angiography (DE-CTA) of the lower extremity runoff compared to standard image reconstruction, using digital subtraction angiography (DSA) as the reference standard. METHODS: Eighty-eight patients (53 males; mean age, 65.9 ± 11 years) with suspected peripheral arterial disease (PAD) who had undergone a DE-CTA examination of the lower extremity runoff between May 2014 and May 2015 were included in this IRB-approved, HIPAA-compliant retrospective study. Standard linearly blended and CS images were reconstructed and vascular contrast-to-noise ratios (CNR) were calculated. Two independent observers assessed subjective image quality using a 5-point Likert scale. Diagnostic accuracy for ≥ 50% stenosis detection was analyzed in a subgroup of 45 patients who had undergone additional DSA. Diagnostic accuracy parameters were estimated with a random-effects logistic regression analysis and compared using generalized estimating equations. RESULTS: CS datasets showed higher CNR (15.3 ± 7.3) compared to standard reconstructions (13.5 ± 6.5, p < 0.001). Both reconstructions showed comparable qualitative image quality scores (CS, 4.64; standard, 4.57; p = 0.220). Diagnostic accuracy (sensitivity, specificity, positive and negative predictive values) for CS reconstructions was 96.5% (97.5%, 95.6%, 90.9%, 98.1) and 93.1% (98.8%, 90.4%, 82.3%, 99.1%) for standard images. CONCLUSIONS: A modified three-material decomposition CS algorithm provides increased vascular CNR, equivalent qualitative image quality, and greater diagnostic accuracy for the detection of significant arterial stenosis of the lower extremity runoff on DE-CTA compared with standard image reconstruction. KEY POINTS: • Calcified plaques may lead to overestimation of stenosis severity and false positive results, requiring additional invasive digital subtraction angiography (DSA). • A modified three-material decomposition algorithm for calcium subtraction provides greater diagnostic accuracy for the detection of significant arterial stenosis of the lower extremity runoff compared with standard image reconstruction. • The application of this algorithm in patients with heavily calcified vessels may be helpful to potentially reduce inconclusive CT angiography examinations and the need for subsequent invasive DSA.

Comparison of Radiation Dose and Image Quality of Contrast-Enhanced Dual-Source CT of the Chest: Single-Versus Dual-Energy and Second-Versus Third-Generation Technology.

OBJECTIVE: The purpose of this study was to compare radiation dose and image quality of single- and dual-energy CT (SECT, DECT) examinations of the chest in matched cohorts for second and third-generation dual-source CT (DSCT) systems. MATERIALS AND METHODS: We analyzed 200 patients (100 men; mean age, 61.7 ± 14.8 years old; 100 women, mean age, 59.4 ± 15.1 years old), matched by sex and body mass index, who had undergone clinically indicated contrast-enhanced chest CT. Four study groups, each consisting of 50 patients, were evaluated. Contrast-enhanced chest CT was performed using vendor-preset second-generation DSCT (group A, 120-kV SECT; group C, 80/Sn140-kV DECT) or third-generation DSCT (group B, 90-kV SECT; group D, 90/Sn150-kV DECT) protocols. Radiation dose assessment was normalized to a scan range of 27.5 cm. Image quality was objectively analyzed using dose-independent figure-of-merit (FOM) contrast-to-noise ratio (CNR) calculations and subjectively evaluated by three independent radiologists. RESULTS: Direct comparison of effective radiation dose for second-generation DSCT groups A and C showed statistically significant lower radiation dose values for DECT compared with SECT acquisition (3.2 ± 1.2 mSv vs 2.3 ± 0.6 mSv, p ≤ 0.004), but differences between third-generation SECT and DECT were not significant (1.2 ± 0.9 mSv vs 1.3 ± 0.6 mSv, p = 0.412). FOM CNR analysis revealed highest values for third-generation DECT (p ≤ 0.043). Differences in subjective image quality between the four groups were not statistically significant (p ≥ 0.179). CONCLUSION: Contrast-enhanced DECT examinations of the chest can be performed routinely with second- and third-generation DSCT systems without either increased radiation exposure or decreased image quality compared with SECT acquisition.

Evaluation of a Computer-Aided Diagnosis System for Automated Bone Age Assessment in Comparison to the Greulich-Pyle Atlas Method: A Multireader Study.

OBJECTIVE: The aim of this study was to investigate a novel version of a computer-aided diagnosis (CAD) system developed for automated bone age (BA) assessment in comparison to the Greulich and Pyle method, regarding its accuracy and the influence of carpal bones on BA assessment. METHODS: Total BA, BA of the left distal radius, and BA of carpal bones in 305 patients were determined independently by 3 blinded radiologists and assessed by the CAD system. Pearson product-moment correlation, Bland-Altman plot, root-mean-square deviation, and further agreement analyses were computed. RESULTS: Mean total BA and BA of the distal radius showed high correlation between both approaches (r = 0.985 and r = 0.963). There was significantly higher correlation between values of total BA and BA of the distal radius (r = 0.969) compared with values of total BA and BA of carpal bones (r = 0.923). The assessment of carpal bones showed significantly lower interreader agreement compared with measurements of the distal radius (κ = 0.79 vs κ = 0.98). CONCLUSION: A novel version of a CAD system enables highly accurate automated BA assessment. The assessment of carpal bones revealed lower precision and interreader agreement. Therefore, methods determining BA without analyzing carpal bones may be more precise and accurate.

Tailored carbon partitioning for phototrophic production of (E)-α-bisabolene from the green microalga Chlamydomonas reinhardtii.

Photosynthetic microbial hosts such as cyanobacteria and eukaryotic microalgae have recently emerged as alternative engineering platforms for the sustainable light-driven bio-production of terpenoids. Many desirable compounds with numerous applications can be produced in microorganisms by heterologous expression of terpene synthases. However, success of green microbial systems has been hampered by issues such as insufficient enzyme expression titers and low flux to desired terpenoid products from carbon fixed during photosynthesis. This work demonstrates how the green microalga Chlamydomonas reinhardtii can be engineered to produce the sesquiterpene biodiesel precursor (E)-α-bisabolene. Through strategic genetic engineering, substantial enhancements of productivity were achieved by coordinated tuning of the isoprenoid metabolism, combining serial enzyme loading for terpene synthase overexpression and amiRNA-based repression of competing pathways. Up to 10.3 ± 0.7mg bisabolene·g-1 cell dry weight could be produced in five days, which represents more than a 15-fold increase over single synthase expression strains. Investigation of strain performance in scale-up cultivations determined overall bisabolene productivity benefits from light:dark cycles. Mixotrophic cultivation can yield up to 11.0 ± 0.5mg bisabolene per liter in seven days in these conditions, and phototrophic production of 3.9 ± 0.2mg per liter was feasible. These achievements represent an important milestone in the engineering of C. reinhardtii towards the goal of designing sustainable, light-driven, green-cell algal bio-factories.

Synthetic metabolic pathways for photobiological conversion of CO2 into hydrocarbon fuel.

Liquid fuels sourced from fossil sources are the dominant energy form for mobile transport today. The consumption of fossil fuels is still increasing, resulting in a continued search for more sustainable methods to renew our supply of liquid fuel. Photosynthetic microorganisms naturally accumulate hydrocarbons that could serve as a replacement for fossil fuel, however productivities remain low. We report successful introduction of five synthetic metabolic pathways in two green cell factories, prokaryotic cyanobacteria and eukaryotic algae. Heterologous thioesterase expression enabled high-yield conversion of native fatty acyl-acyl carrier protein (ACP) into free fatty acids (FFA) in Synechocystis sp. PCC 6803 but not in Chlamydomonas reinhardtii where the polar lipid fraction instead was enhanced. Despite no increase in measurable FFA in Chlamydomonas, genetic recoding and over-production of the native fatty acid photodecarboxylase (FAP) resulted in increased accumulation of 7-heptadecene. Implementation of a carboxylic acid reductase (CAR) and aldehyde deformylating oxygenase (ADO) dependent synthetic pathway in Synechocystis resulted in the accumulation of fatty alcohols and a decrease in the native saturated alkanes. In contrast, the replacement of CAR and ADO with Pseudomonas mendocina UndB (so named as it is responsible for 1-undecene biosynthesis in Pseudomonas) or Chlorella variabilis FAP resulted in high-yield conversion of thioesterase-liberated FFAs into corresponding alkenes and alkanes, respectively. At best, the engineering resulted in an increase in hydrocarbon accumulation of 8- (from 1 to 8.5 mg/g cell dry weight) and 19-fold (from 4 to 77 mg/g cell dry weight) for Chlamydomonas and Synechocystis, respectively. In conclusion, reconstitution of the eukaryotic algae pathway in the prokaryotic cyanobacteria host generated the most effective system, highlighting opportunities for mix-and-match synthetic metabolism. These studies describe functioning synthetic metabolic pathways for hydrocarbon fuel synthesis in photosynthetic microorganisms for the first time, moving us closer to the commercial implementation of photobiocatalytic systems that directly convert CO2 into infrastructure-compatible fuels.