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Biomedical subjects

Thomas Flohr

Publications and source records attributed to Thomas Flohr.

At least 19 recordsLinked to original sources

Minimal residual disease analysis in children with t(12;21)-positive acute lymphoblastic leukemia: comparison of Ig/TCR rearrangements and the genomic fusion gene.

Quantification of minimal residual disease (MRD) based on clonotypic immunoglobulin/ T-cell receptor (Ig/TCR) gene rearrangements is widely used as an independent prognostic parameter in childhood acute lymphoblastic leukemia (ALL). In this study we compared MRD by quantification of Ig/TCR targets and genomic ETV6-RUNX1 specific sequences. In ten of twelve patients with t(12;21)+ ALL we observed concordance with rapid blast reduction in nine, and high-level persistence in one case. The two remaining patients showed low-level persistence of the genomic breakpoint specific sequence. These patients have remained in complete remission for 38 and 41 months, so far, indicating that a small ETV6-RUNX1-positive clone is not detrimental to the short-term prognosis of affected children.

Antineoplastic Combined Chemotherapy Protocols↗

Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia.

Activating mutations of the transmembrane receptor NOTCH1 are common in precursor T-cell lymphoblastic leukemia (T-ALL). We systematically analyzed the impact of activating NOTCH1 mutations on early treatment response and long-term outcome in 157 patients with T-ALL of the pediatric ALL-Berlin-Frankfurt-Munster (BFM) 2000 study. We confirm previous results that NOTCH1 mutations occur in more than 50% of T-ALL in children. In 82 patients (82/157; 52.2%), activating NOTCH1 mutations were identified either in the heterodimerization (55/82; 67.1%), in the PEST (13/82; 15.9%), or in both domains (14/82; 17.0%). The presence of NOTCH1 mutations was significantly correlated with a good prednisone response and favorable minimal residual disease (MRD) kinetics, which was independent from sex, age, white blood cell count, and T-cell immunophenotype at the time of diagnosis. Furthermore, activating NOTCH1 mutations specified a large subgroup of patients with an excellent prognosis. These findings indicate that in the context of the ALL-BFM 2000 treatment strategy, NOTCH1 mutations predict a more rapid early treatment response and a favorable long-term outcome in children with T-ALL.

Adolescent↗

Ultra-high resolution flat-panel volume CT: fundamental principles, design architecture, and system characterization.

Digital flat-panel-based volume CT (VCT) represents a unique design capable of ultra-high spatial resolution, direct volumetric imaging, and dynamic CT scanning. This innovation, when fully developed, has the promise of opening a unique window on human anatomy and physiology. For example, the volumetric coverage offered by this technology enables us to observe the perfusion of an entire organ, such as the brain, liver, or kidney, tomographically (e.g., after a transplant or ischemic event). By virtue of its higher resolution, one can directly visualize the trabecular structure of bone. This paper describes the basic design architecture of VCT. Three key technical challenges, viz., scatter correction, dynamic range extension, and temporal resolution improvement, must be addressed for successful implementation of a VCT scanner. How these issues are solved in a VCT prototype and the modifications necessary to enable ultra-high resolution volumetric scanning are described. The fundamental principles of scatter correction and dose reduction are illustrated with the help of an actual prototype. The image quality metrics of this prototype are characterized and compared with a multi-detector CT (MDCT).

Algorithms↗

High-resolution ex vivo imaging of coronary artery stents using 64-slice computed tomography--initial experience.

The aim of the study was to evaluate the potential of new-generation multi-slice computed tomography (CT) scanner technology for the delineation of coronary artery stents in an ex vivo setting. Nine stents of various diameters (seven stents 3 mm, two stents 2.5 mm) were implanted into the coronary arteries of ex vivo porcine hearts and filled with a mixture of an iodine-containing contrast agent. Specimens were scanned with a 16-slice CT (16SCT) machine; (Somatom Sensation 16, Siemens Medical Solutions), slice thickness 0.75 mm, and a 64-slice CT (64SCT, Somatom Sensation 64), slice-thickness 0.6 mm. Stent diameters as well as contrast densities were measured, on both the 16SCT and 64SCT images. No significant differences of CT densities were observed between the 16SCT and 64SCT images outside the stent lumen: 265+/-25HU and 254+/-16HU (P=0.33), respectively. CT densities derived from the 64SCT images and 16SCT images within the stent lumen were 367+/-36HU versus 402+/-28HU, P<0.05, respectively. Inner and outer stent diameters as measured from 16SCT and 64SCT images were 2.68+/-0.08 mm versus 2.81+/-0.07 mm and 3.29+/-0.06 mm versus 3.18+/-0.07 mm (P<0.05), respectively. The new 64SCT scanner proved to be superior in the ex vivo assessment of coronary artery stents to the conventional 16SCT machine. Increased spatial resolution allows for improved assessment of the coronary artery stent lumen.

Animals↗

Contrast-enhanced coronary artery visualization by dual-source computed tomography--initial experience.

UNLABELLED: Multi-detector computed tomography (CT) scanners, by virtue of their high temporal and spatial resolution, permit imaging of the coronary arteries. However, motion artifacts, especially in patients with higher heart rates, can impair image quality. We thus evaluated the performance of a new dual-source CT (DSCT) with a heart rate independent temporal resolution of 83 ms for the visualization of the coronary arteries in 14 consecutive patients. METHODS: Fourteen patients (mean age 61 years, mean heart rate 71 min(-1)) were studied by DSCT. The system combines two arrays of an X-ray tube plus detector (64 slices) mounted on a single gantry at an angle of 90 degrees With a rotation speed of 330 ms, a temporal resolution of 83 ms (one-quarter rotation) can be achieved independent of heart rate. For data acquisition, intraveous contrast agent was injected at a rate of 5 ml/s. Images were reconstructed with 0.75 slice thickness and 0.5 mm increment. The data sets were evaluated concerning visibility of the coronary arteries and occurrence of motion artifact. RESULTS: Visualization of the coronary arteries was successful in all patients. Most frequently, image reconstruction at 70% of the cardiac cycle provided for optimal image quality (50% of patients). Of a total of 226 coronary artery segments, 222 (98%) were visualized free of motion artifact. In summary, DSCT constitutes a promising new concept for cardiac CT. High and heart rate independent temporal resolution permits imaging of the coronary arteries without motion artifacts in a substantially increased number of patients as compared to earlier scanner generations. Larger and appropriately designed studies will need to determine the method's accuracy for detection of coronary artery stenoses.

Artifacts↗

64- Versus 16-slice CT angiography for coronary artery stent assessment: in vitro experience.

OBJECTIVES: We sought to assess the visualization of different coronary artery stents and the delineation of in-stent stenoses using 64- and 16-slice multidector computed tomography (MDCT). MATERIALS AND METHODS: A total of 15 different coronary stents with a simulated in-stent stenosis were placed in a vascular phantom and scanned with a 16-slice and a 64-slice MDCT at orientations of 0 degree, 45 degrees, and 90 degrees relative to the scanner's z-axis. Visible lumen diameter and attenuation in the stented and the unstented segment of the phantom were measured. Three readers assessed stenosis delineation and visualization of the residual lumen using a 5-point scale. RESULTS: Artificial lumen narrowing (ALN) was significantly reduced with 64-slice CT compared with 16-slice CT. At an angle of 0 degree, 45 degrees, and 90 degrees relative to the scanner's z-axis, the ALN for 16-slice CT was 42.2%, 39.8%, and 44.0% using a slice-thickness of 1.0 mm and 40.9%, 40.4%, and 41.6% using a slice thickness of 0.75 mm, respectively. With 64-slice CT, the ALN was 39.1%, 37.3%, and 36.0% at the respective angles. The differences between attenuation values in the stented and unstented segment of the tube were significantly lower for 64-slice CT. Mean visibility scores were significantly higher for 64-slice CT. CONCLUSION: Use of the 64-slice CT results in superior visualization of the stent lumen and in-stent stenosis compared with 16-slice CT, especially when the stent is orientated parallel to the x-ray beam.

Coronary Angiography↗

Image quality, motion artifacts, and reconstruction timing of 64-slice coronary computed tomography angiography with 0.33-second rotation speed.

OBJECTIVES: We sought to evaluate the impact of patients' heart rate (HR) on coronary CTA image quality (IQ) and motion artifacts using a 64-slice scanner with 0.33/360 degrees rotation. MATERIALS AND METHODS: Coronary CTA data sets of 32 patients (HR 65 bpm to 75 bpm, n = 7) examined on a 64-slice scanner (Sensation 64, Siemens Medical Solutions, Forchheim, Germany) with 0.33s/360 degrees gantry rotation speed were analyzed. All patients had suspicion of coronary artery disease. Data acquisition was performed using 64 x 0.6-mm collimation, and contrast enhancement was provided by injection of 80 mL of iopromide (5 mL/s + NaCl). Images were reconstructed throughout the RR interval using half-scan and dual-segment reconstruction. IQ was rated by 2 observers using a 3-point scale from excellent (1) to nondiagnostic (3) for coronary segments. Quality was correlated to the HR, time point of optimal IQ analyzed, and the benefit of dual-segment reconstruction evaluated. RESULTS: Overall mean IQ was 1.31 +/- 0.32 for all HR, with IQ being 1.08 +/- 0.12 for HR 65 bpm 75 bpm (P = 0.0003). Dual-segment reconstruction did not significantly improve IQ in any HR group (P = NS). Mean IQ was significantly better for LAD than for RCA (P < 0.0001) and LCX (P < 0.01). A total of 3.5% (11/318) of coronary artery segments were rated nondiagnostic by at least one reader based on motion artifacts. Although in HR < 65 bpm, the best IQ was predominately in diastole (93%), in HR > 75 bpm, the best IQ shifted to systole in most cases (86%). CONCLUSIONS: Temporal resolution at 0.33-second rotation allows for diagnostic IQ within a wide range of HR using half-scan reconstruction. With increasing HR the time point of best IQ shifts from mid-diastole to systole.

Adult↗

Comparison of angular and combined automatic tube current modulation techniques with constant tube current CT of the abdomen and pelvis.

OBJECTIVE: The objective of our study was to compare image quality and radiation dose associated with abdominopelvic CT using combined modulation, angular modulation, and constant tube current. CONCLUSION: Compared with using a constant tube current to scan the abdomen and pelvis, the use of a combined modulation technique results in a substantial reduction (42-44%) in radiation dose with acceptable image noise and diagnostic acceptability.

Adult↗

64-slice multidetector coronary CT angiography: in vitro evaluation of 68 different stents.

The purpose of this study was to test a large sample of different coronary artery stents using four image reconstruction approaches with respect to lumen visualization, lumen attenuation, and image noise in 64-slice multidetector-row computed tomography (MDCT) in vitro and to provide a catalogue of currently used coronary artery stents when imaged with state-of the-art MDCT. We examined 68 different coronary artery stents (57 stainless steel, four cobalt-chromium, one cobalt-alloy, two nitinol, four tantalum) in a coronary artery phantom (vessel diameter 3 mm, intravascular attenuation 250 HU, extravascular density -70). Stents were imaged in axial orientation with standard parameters: 32 x 0.6 collimation, pitch 0.24, 680 mAs, 120 kV, rotation time 0.37 s. Four different image reconstructions were obtained with varying convolution kernels and section thicknesses: (1) soft, 0.6 mm, (2) soft, 0.75, (3) medium soft, 0.6, and (4) stent-optimized sharp, 0.6. To evaluate visualization characteristics of of the stent, the lumen diameter, intraluminal density and noise were measured. The high-resolution kernel offered significantly better average lumen visualization (57% +/-10%) and more realistic lumen attenuation (222 HU +/-66 HU) at the expense of increased noise (15.3 HU +/-3.7 HU) compared with the soft and medium-soft CT angiography (CTA) protocol (p<0.001 for all). Stents with a lumen visibility of more than 66% were: Arthos pico, Driver, Flex, Nexus2, S7, Tenax complete, Vision (all 67%), Symbiot, Teneo (70%), and Radius (73%). Only ten stents showed a lumen visibility of less than 50%. Stent lumen visibility largely varies depending on the stent type. Even with the improved spatial resolution of 64-slice CT, a stent-optimized kernel remains beneficial for stent visualization when compared with the standard medium-soft CTA protocol. Using 64-slice CT and high-resolution kernel, the majority of stent products show a lumen visibility of more than 50% of the stent diameter.

Alloys↗

Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia.

Adult patients with acute lymphoblastic leukemia (ALL) who are stratified into the standard-risk (SR) group due to the absence of adverse prognostic factors relapse in 40% to 55% of the cases. To identify complementary markers suitable for further treatment stratification in SR ALL, we evaluated the predictive value of minimal residual disease (MRD) and prospectively monitored MRD in 196 strictly defined SR ALL patients at up to 9 time points in the first year of treatment by quantitative polymerase chain reaction (PCR). Frequency of MRD positivity decreased from 88% during early induction to 13% at week 52. MRD was predictive for relapse at various follow-up time points. Combined MRD information from different time points allowed definition of 3 risk groups (P < .001): 10% of patients with a rapid MRD decline to lower than 10(-4) or below detection limit at day 11 and day 24 were classified as low risk and had a 3-year relapse rate (RR) of 0%. A subset of 23% with an MRD of 10(-4) or higher until week 16 formed the high-risk group, with a 3-year RR of 94% (95% confidence interval [CI] 83%-100%). The remaining patients whose RR was 47% (31%-63%) represented the intermediate-risk group. Thus, MRD quantification during treatment identified prognostic subgroups within the otherwise homogeneous SR ALL population who may benefit from individualized treatment.

Adolescent↗

Four-dimensional multislice computed tomography for determination of respiratory lung tumor motion in conformal radiotherapy.

PURPOSE: We used four-dimensional multislice spiral computed tomography (MSCT) to determine respiratory lung-tumor motion and compared this strategy to common clinical practice in conformal radiotherapy treatment-planning imaging. METHODS AND MATERIALS: The entire lung volume of 10 consecutive patients with 14 lung metastases were scanned by a 16-slice MSCT. During the scans, patients were instructed to breathe through a spirometer that was connected to a laptop computer. For each patient, 10 stacks of 1.5-mm slices, equally distributed throughout the respiratory cycle, were reconstructed from the acquired MSCT data. The lung tumors were manually contoured in each data set. For each patient, the tumor-volume contours of all data sets were copied to 1 data set, which allowed determination of the volume that encompassed all 10 lung-tumor positions (i.e., the tumor-traversed volume [TTV]) during the respiratory cycle. The TTV was compared with the 10 tumor volumes contoured for each patient, to which an empiric respiratory-motion margin was added. The latter target volumes were designated internal-motion included tumor volume (IMITV). RESULTS: The TTV measurements were significantly smaller than the reference IMITV measurements (5.2 +/- 10.2 cm(3) and 10.1 +/- 13.7 cm(3), respectively). All 10 IMITVs for 2 of the 4 tumors in 1 subject completely encompassed the TTV. All 10 IMITVs for 3 tumors in 2 patients did not show overlap with up to 35% of the corresponding TTV. The 10 IMITVs for the remaining tumors either completely encompassed the corresponding TTV or did not show overlap with up to 26% of the corresponding TTV. CONCLUSIONS: We found that individualized determination of respiratory lung-tumor motion by four-dimensional respiratory-gated MSCT represents a better and simple strategy to incorporate periodic physiologic motion compared with a generalized approach. The former strategy can, therefore, improve common and state-of-the-art clinical practice in conformal radiotherapy.

Aged↗

Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia.

CONTEXT: Early response to multiagent chemotherapy, including mercaptopurine, as measured by minimal residual disease is an important prognostic factor for children with acute lymphoblastic leukemia (ALL). Thiopurine methyltransferase (TPMT) is involved in the metabolism of mercaptopurine and subject to genetic polymorphism, with heterozygous individuals having intermediate and homozygous mutant individuals having very low TPMT activity. OBJECTIVE: To assess the association of TPMT genotype with minimal residual disease load before and after treatment with mercaptopurine in the early treatment course of childhood ALL. DESIGN, SETTING, AND PATIENTS: TPMT genotyping of childhood ALL patients (n = 814) in Germany consecutively enrolled in the ALL-BFM (Berlin-Frankfurt-Münster) 2000 study from October 1999 to September 2002. Minimal residual disease was analyzed on treatment days 33 and 78 for risk-adapted treatment stratification. A 4-week cycle of mercaptopurine was administered between these 2 minimal residual disease measurements. Patients (n = 4) homozygous for a mutant TPMT allele, and consequently deficient in TPMT activity, were treated with reduced doses of mercaptopurine and, therefore, not included in the analyses. MAIN OUTCOME MEASURES: Minimal residual disease load before (day 33) and after (day 78) mercaptopurine treatment. Loads smaller than 10(-4) were defined as negative. RESULTS: Patients (n = 55) heterozygous for allelic variants of TPMT conferring lower enzyme activity had a significantly lower rate of minimal residual disease positivity (9.1%) compared with patients (n = 755) with homozygous wild-type alleles (22.8%) on day 78 (P = .02). This translated into a 2.9-fold reduction in risk for patients with wild-type heterozygous alleles (relative risk, 0.34; 95% confidence interval, 0.13-0.86). CONCLUSIONS: TPMT genotype has a substantial impact on minimal residual disease after administration of mercaptopurine in the early course of childhood ALL, most likely through modulation of mercaptopurine dose intensity. Our findings support a role for minimal residual disease analyses in the assessment of genotype-phenotype associations in multiagent chemotherapeutic trials.

Adolescent↗

Assessment of coronary artery stents using 16-slice MDCT angiography: evaluation of a dedicated reconstruction kernel and a noise reduction filter.

To compare the effect of different reconstruction kernels and a noise-reducing postprocessing filter on the delineation of coronary artery stents in 16-slice CT-angiography. Ten patients with coronary stents (seven LAD, five RCX and three RCA) were examined with a 16-slice MDCT using standard acquisition parameters. Images were reconstructed using a medium soft (B30f) and a dedicated, edge-enhancing kernel (B46f). Additional postprocessing with an edge-preserving filter was performed on B46f images to reduce the image noise. In multiplanar reformations (MPRs) along and perpendicular to the stent axis, intraluminal attenuation values and the visible lumen diameter were measured. Image noise was measured in the subcutaneous fat using a region of interest (ROI) technique. Arterial enhancement in the aorta was 275.1 HU. Attenuation in the stent lumen was 390.4, 340.0 and 346.8 HU in MPRs derived from B30f, original B46 and postprocessed B46f images. The mean noise level was 20.4, 35.0 and 24.9 HU respectively. The visible lumen diameter was significantly greater in B46f and postprocessed B46f images (2.17 and 2.16 mm), compared to 1.93 mm in B30f images (p<0.01). Edge-enhancing reconstruction kernels increase the visible stent lumen, but also increase image noise. Dedicated postprocessing filters can reduce the introduced noise without a loss of spatial resolution.

Artifacts↗

Metallic prosthesis: technique to avoid increase in CT radiation dose with automatic tube current modulation in a phantom and patients.

The institutional review board approved this Health Insurance Portability and Accountability Act-compliant study protocol, with waiver of informed consent. The purpose of the study was to retrospectively evaluate the combined automatic tube current modulation technique in patients with orthopedic metallic prostheses. Five hundred abdominal-pelvic computed tomographic (CT) studies performed with combined modulation technique were reviewed to identify nine patients with metallic prostheses (mean age, 66 years; range, 35-86 years; male-female ratio, 5:4). On the basis of age and transverse abdominal images, these patients were matched with nine others with no metallic prostheses (mean age, 56 years; range, 36-72 years; male-female ratio, 4:5) who were control patients. Images were graded for extent and severity of streak artifacts (grade 1, streak artifact present but not substantially compromising evaluation of adjacent structures; grade 2, streak artifact present and slightly compromising evaluation of adjacent structures; and grade 3, streak artifact present and severely compromising evaluation of adjacent structures). Student t test was performed for statistical analysis. There was no difference in mean effective tube current-time product between study and control patients (P > .49). With automatic tube current modulation, an increase in CT dose caused by metallic prostheses can be successfully avoided.

Adult↗

Optimization of MDCT of the wrist to achieve diagnostic image quality with minimum radiation exposure.

OBJECTIVE: This study tests various acquisition and reconstruction protocols for MDCT of the wrist to determine the optimal protocol for obtaining diagnostic image quality with minimal radiation exposure. MATERIALS AND METHODS: Thirty anatomic specimens were examined with an MDCT collimation of 4.0 x 1.0 mm and 2.0 x 0.5 mm (80, 120, and 140 kV; 80, 100, 130, 160, and 200 mA; rotation time, 0.5 0.75, 1.0 sec; pitch, 1.0, 1.3, 1.5, and 2.0). Coronal images were reconstructed using a slice thickness of 0.5, 1.0, and 2.0 mm with 60% overlap. Three observers evaluated all images independently for gross and fine anatomic detail. Diagnostic confidence was tested using Shrout-Fleiss intraclass correlation coefficients. Interobserver agreement was assessed by Kappa statistics and the Kruskal-Wallis test. RESULTS: Fine anatomic detail was best presented in 0.5-mm or 1.00-mm reconstructions based on a 2.0 x 0.5 mm acquisition. A rotation time of > or = 0.75 sec resulted in fewer artifacts; a significant dose reduction was achieved with 80 kV and 100 mA at the expense of somewhat increased noise, but without significant loss of anatomic detail in bone presentation. Artifacts were tolerable with a pitch of 1.5 or less. CONCLUSION: MDCT at the described optimal settings allows significant dosage reduction without sacrificing image quality. An acquisition and reconstruction thickness of 0.5 mm results in the best depiction of anatomic detail. A reconstruction thickness of 1.0 mm with a reconstruction interval of 0.5 mm represents a good trade-off between noise and resolution when using low-dose protocols.

Aged↗

Flat-panel detector computed tomography for the assessment of coronary artery stents: phantom study in comparison with 16-slice spiral computed tomography.

PURPOSE: The evaluation of coronary artery stents is a major limitation of cardiac multislice spiral computed tomography (MSCT). The development of flat-panel detector computed tomography (FPCT) with truly isotropic spatial resolution may overcome this limitation. Thus, we evaluated the use of FPCT in comparison to MSCT for the assessment of coronary artery stents. MATERIAL AND METHODS: Eight different coronary artery stents with a diameter of 3 mm each were placed in a static chest phantom. The phantom was positioned in the CT gantry at angles of 0 degrees , 45 degrees , and 90 degrees toward the z-axis and examined with the prototype of a FPCT (Siemens, Forchheim, Germany) and a commercially available 16-detector row MSCT (Sensation 16, Siemens). Slice thickness was 0.25 mm with FPCT whereas for MSCT, an effective slice thickness of 1 mm with a reconstruction increment of 0.5 mm was used. Image quality was assessed visually using a 5-point grading scale. Stent diameters were measured and compared using a repeated-measures analysis of variance. RESULTS: When compared with MSCT, artificial lumen reduction was significantly less using FPCT. On average the visible stent lumen was reduced by 16.1% with FPCT, whereas the mean of the lumen reduction was 47.2% with 16-detector row MSCT. Visible lumen diameter as well as image noise significantly increased using FPCT (P < 0.001). With FPCT delineation of the different stent struts became possible. CONCLUSION: FPCT proved to be superior when compared with 16-detector row MSCT for the in vitro assessment of coronary artery stents. Improved spatial resolution allows for a detailed assessment of the coronary artery stent lumen.

Coronary Angiography↗

Coronary arteries: assessment of image quality and optimal reconstruction window in retrospective ECG-gated multislice CT at 375-ms gantry rotation time.

Our objective was to evaluate the image quality of a 16-slice CT system with a rotation time of 375 ms in the assessment of coronary arteries. One hundred patients underwent iodine-enhanced CT coronary angiography within a single breath hold. Images were reconstructed in diastole, 300, 350, 400, 450, 500 and 550 ms prior to the onset of the next R-wave using absolute reverse retrospective ECG gating. The 15 coronary segments of the AHA classification were consensually reviewed by two radiologists. On the whole, best quality imaging was obtained with reconstruction intervals of -350 ms and -400 ms in high percentages of each segment (P<0.0001). Only 6.2% of the arteries with a diameter greater than or equal to 1.5 mm were not assessable because of extensive calcifications (3.9%), cardiac motion artifacts (1.9%), lack of enhancement (0.2%) and stent artifacts (0.3%). In patients with a heart rate above 70 beats per minute, the percentage of assessable segments decreased to 88%, while at a lower heart rate it increased to 95%. In 61% of the patients, all segments were assessable. In conclusion, this generation of CT technique may allow visualization of coronary arteries with a low percentage of non-assessable segments.

Adult↗