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Gastrointestinal Imaging |
1 From the Department of Diagnostic and Interventional Radiology (T.S., H.K.) and Department of General Surgery and Transplantation (A.R., M.M.), University Hospital Essen, Hufelandstrasse 55, D-45122 Essen, Germany; University Hospital Eppendorf, Hamburg, Germany (J.F.D.); and Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, Calif (S.G.R.). Received January 27, 2005; revision requested March 31; revision received April 15; accepted May 19; manuscript final version approval May 31. Supported in part by the German Research Society, Bonn, Germany, Grant KFO 117/1-1;A2.2. Address correspondence to T.S. (e-mail: Tobias.Schroeder{at}uni-essen.de).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Materials and Methods: A total of 250 potential living liver donors (112 women, 138 men; mean age, 37 years) underwent three-phase, dual-enhancement multi–detector row CT to delineate biliary, vascular, and parenchymal morphology according to an institutional review board–approved protocol. Informed consent was obtained from all subjects. For display of the biliary system, the first CT image set was collected after the infusion of a biliary contrast agent. CT angiography was subsequently performed, after automated injection of a conventional iodinated contrast agent, to display the arterial and portal-hepatic venous systems. All data sets were reconstructed in 1-mm sections. Data analysis was based on source images, multiplanar reconstructions, and three-dimensional postprocessing images; was performed in consensus by two radiologists; and was focused on the detection of biliary and vascular variants, exclusion of focal liver lesions, and determination of hepatic volumes. Preoperative findings were correlated with intraoperative findings (available in 62 subjects).
Results: Technical failures were experienced in 10 of 250 examinations. Twenty-seven subjects had moderate adverse reactions related to the biliary contrast agent. Benign hepatic lesions were detected in 61 candidates; one candidate had a renal cell carcinoma. Underlying biliary and vascular anatomy was displayed at least to the second intrahepatic branch in all but seven patients. Detected anatomic variants involved the biliary (38.8%), arterial (40.0%), portal venous (21.4%), and hepatic venous (43.5%) systems. Correlation with intraoperative findings was excellent. Some biliary (n = 4), arterial (n = 5), portal venous (n = 1), and hepatic venous (n = 6) variants were missed or misinterpreted at initial reading of preoperative data; however, variants could be retrospectively depicted in all but one biliary case and one hepatic venous case.
Conclusion: The outlined three-phase, dual-enhancement multi–detector row CT protocol represents an all-inclusive approach to evaluate potential living liver donors in a single diagnostic step.
© RSNA, 2006
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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This innovative procedure allows healthy adults to donate a portion of their livers to compatible recipients with endstage liver disease (3–5).
Besides augmenting the transplant organ pool, living donor liver transplantation provides the advantages of performing an elective operation, having access to a graft in best condition, and lowering the likelihood of recipient death while waiting for a suitable organ (6). Supported by improved surgical technique and immunosuppression (7), living donor liver transplantation results in recipient survival rates comparable with those obtained after conventional liver transplantation with full-sized cadaveric organs (8). In addition, living donor liver transplantation offers the possibility of liver replacement to selected patients who might be ineligible for cadaveric organ transplantation (9).
A critical issue of this procedure remains the risk it imposes on the healthy donors, which is reflected in a postoperative morbidity rate of 21% and a mortality rate of 0.5% (1,10–13). One reason for this drawback is seen in a high number of either unrecognized or, during the operation, extemporaneously handled biliary and vascular variants (14). To reduce such risk to a minimum, and also to ensure optimal surgical results in the recipient, the donation candidates have to undergo an extensive stepwise-fashioned evaluation process before being admitted for donation. After overcoming the psychologic barriers of agreeing to donate part of an organ, the thorough anatomic study of the donor's liver is of major importance. Special attention is given to the determination of the liver volumes (15–18) and the recognition of vascular and biliary anomalies (19–23). In fact, a majority of the candidates are eliminated mostly because of unfavorable hepatic parenchymal, biliary, or vascular morphology (24–26).
Conventionally, the preharvest assessment employs a multimodality radiologic evaluation protocol, including computed tomography (CT) or magnetic resonance (MR) imaging for liver planimetry to determine transplant volumes and exclude parenchymal lesions, catheter digital subtraction angiography to display the hepatic vascular system, endoscopic retrograde cholangiopancreatography to assess the biliary anatomy, and liver biopsy to assess fatty hepatic-cellular infiltration (24,25).
To simplify and shorten such time-consuming and costly (27,28) procedures, reports in the literature support the use of multi–detector row CT as a comprehensive evaluation tool to combine the advantage of minimal invasiveness with simultaneous assessment of the hepatic parenchymal morphology and detailed analysis of the vascular (29) and biliary (30) anatomy.
The purpose of our study, therefore, was to prospectively assess the parenchymal, vascular, and biliary anatomy of potential living liver donors in an all-inclusive multi–detector row CT approach.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Multi–Detector Row CT Protocol
CT was performed by using a four–detector row CT scanner (until July 2002: Volume-Zoom, Siemens, Erlangen, Germany) in 88 subjects (35.2%) and by using a 16–detector row CT scanner (after July 2002: Sensation 16, Siemens) in 162 subjects (64.8%). The multi–detector row CT protocol included successive acquisition of three image sets of the liver by using the parameters summarized in Table 1.
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CT angiography was subsequently performed to display the hepatic arterial anatomy. For this purpose, 140 mL of a conventional iodinated contrast agent (iomeprol, Imeron 350; Bracco, Milan, Italy) was administered intravenously by using an automated injector (CT9000, Liebel-Flarsheim, Cincinnati, Ohio or EmpowerCTA, E-Z-Em, New York, NY) at a rate of 5 mL/sec. Automated bolus tracking with bolus detection at the level of the ascending aorta ensured accurate timing of the data acquisition in an early arterial phase. For the display of the portal and hepatic venous anatomy, a third CT image set was acquired, with an effective delay of 55–65 seconds after initiation of the contrast material injection. All contrast material was administered through an antecubital venous catheter with a minimum size of 20 gauge.
Each image set was collected within one breath hold over 20–25 seconds (with the four–detector row scanner) or 10–15 seconds (with the 16–detector row scanner). Both the time in the CT scanner room (the "in-room" time) and the time needed for postprocessing of the imaging data and image interpretation were measured. To determine the presence of any adverse reactions related to the contrast agent administration, all subjects remained under medical observation for at least 1 hour after the CT examination was completed.
Image Interpretation
Analysis of the image data was based on source images and three-dimensional (3D) postprocessing images (maximum intensity projections and shaded surface image reconstructions for instant overview of the biliary and vascular morphology, volume renderings for the final assessment and documentation). All data were postprocessed on a commercially available workstation (Virtuoso; Siemens). To provide a more realistic 3D impression, the reconstructed 3D images were also reviewed stereoscopically, which included visual enhancement by means of artificial coloring (32). Data interpretation was based on consensus of two radiologists (T.S. and S.G.R., with 8 and 11 years of experience, respectively) in conjunction with two transplant surgeons (A.R. and M.M., with more than 11 and more than 20 years of experience, respectively) who were also familiar with the review technique. Image analysis was focused on the following aspects:
Assessment of CT study as diagnostic versus nondiagnostic.—The study was regarded as diagnostic when both the biliary and the vascular structures were sufficiently contrast-enhanced to allow reliable determination or exclusion of anatomic variants, particularly with respect to the surgical procedure.
Exclusion of focal liver lesions.—The hepatic parenchyma was assessed for the presence of masses on the basis of all three collected image sets. Other organs were similarly assessed for concomitant disease.
Size of hepatic lobes.—Hepatic volumes were determined by manually tracing the contours of both the entire liver and the graft (liver segments V–VIII) on the venous image set, excluding the inferior vena cava and the gallbladder fossa. To facilitate calculation of hepatic volumes, the sections were divided into contiguous, nonoverlapping 10-mm intervals by using planimetry (16,33–35). The virtual hepatectomy plane followed the middle hepatic vein, corresponding to the plane of the performed surgery. To avoid interobserver variability, all volumetric data were determined by means of consensus reading by the same radiologist and transplant surgeon (T.S., A.R.).
Morphology of the biliary system.—The biliary anatomy as displayed on the initial image set was analyzed and assessed for anatomic variants according to the Couinaud classification system (23).
Morphology of the hepatic arterial system.—The arterial anatomy was assessed on the second image set and was analyzed for the presence of anatomic variants, classified according to a system created by Michels (19), by noting the origins of the right and left hepatic arteries and the presence of any accessory hepatic arteries.
Morphology of the portal veins.—The portal venous system was evaluated on the third image set (venous phase images) by separately analyzing the splenic and superior mesenteric vein, the portal vein, and the right and left portal branches. Anatomic variants were characterized according to the classification system of Akgul et al (21).
Morphology of the hepatic veins.—The hepatic veins were also evaluated on the third image set and were characterized according to the classification system of Nakamura and Tsuzuki (22).
Those candidates who were elected as donors underwent liver biopsy, which represents a mandatory step in the local evaluation protocol.
Intraoperative Comparisons
As of December 2004, 62 of the 250 evaluated donation candidates (24.8%; 31 women and 31 men; mean age, 36.2 years) had undergone adult-to-adult living liver donor transplantation surgery. Another three surgical procedures were prematurely cancelled because of either intraoperative recipient death (n = 1) or the presence of until-then unrecognized extrahepatic metastases in the recipient (n = 2).
One hundred two donation candidates (40.8%) were rejected because of unfavorable anatomy. This was most often due to inappropriate hepatic volumes (n = 100). Two candidates were rejected because of the presence of three or more vascular and biliary variants, which was considered a factor for potentially high risk and complications during surgery. Sixteen potential donors (6.4%) were rejected because of diffuse liver disease (eg, steatosis, hepatitis, hemochromatosis). In 61 candidates (24.4%), further evaluation was cancelled because of recipient-related reasons (eg, availability of a cadaveric organ, alternative donors with more suitable volumetric findings, death). In the remaining six candidates, either definite decision or transplantation surgery was still pending at the conclusion of our study.
The preharvest reading of multi–detector row CT data sets regarding the biliary and vascular morphology were compared with intraoperative findings, which served as the standard of reference. The intraoperatively determined graft weights and the preoperatively assessed transplant volumes were compared on the basis of a 1:1.15 conversion factor, which assumes similar physical densities of water and healthy donor liver tissue but also takes into account the aspect of the resected grafts deperfusion (33,36).
Postoperative Follow-up
After surgery the donors remained under clinical observation for 15 days ± 2. Daily clinical examination and blood analysis were performed as part of the clinical routine.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Examination Time
The "in-room" time ranged between 8 and 14 minutes (mean, 10.8 minutes ± 1.5). The total examination time, which included preparation of the candidates and slow infusion of the biliary contrast agent outside the scanner room, ranged between 25 and 45 minutes.
Adverse Reactions
There were no severe adverse reactions observed. However, on completion of the CT examination, 27 (10.8%; 12 women, 15 men) of the 250 subjects had moderate adverse reactions, which included feeling of heat and nausea and also erythema on face and arms. None of those individuals was known to have experienced any kind of allergy or other hypersensitivity before. After treatment with standard antihistaminic medication, the symptoms resolved within 20 minutes.
Image Analysis Time
Image analysis based on both source images and manually optimized postprocessing images, including manual planimetry of hepatic volumes and detailed assessment of the biliary and vascular morphology, required between 18 and 55 minutes (mean, 32.9 minutes ± 6.4).
Liver Parenchyma and Hepatic Volumes
In all but the aforementioned two subjects with mistimed venous phase imaging, the liver parenchyma was visualized with diagnostic quality with high spatial resolution. In 187 subjects, no hepatic parenchymal abnormality was shown. In 61 subjects, at least one sort of incidental hepatic lesion was seen, which was classified as follows: cyst (n = 53), hemangioma (n = 16), adenoma (n = 2), or focal nodular hyperplasia (n = 1; Fig 1). Five candidates—two suspected of having an adenoma, two assumed to have a hemangioma, and one supposed to have focal nodular hyperplasia—underwent diagnostic biopsy, which confirmed the CT findings in all cases. In five candidates, the liver parenchyma showed distinct hypodensity, which was interpreted to be the correlative of an extensive hepatic steatosis. Six candidates had biliary calculi; one candidate showed signs consistent with cholecystitis.
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Considering a multiplication factor of 1.15 to transform the weight of the nonperfused graft into a comparable volume quantity, the intraoperative assessment, which was based on actual weighing, showed values between 601 and 1212 mL (mean, 915 mL ± 159). The difference to the predicted transplant volumes ranged between –139 mL (14.1%) and 182 mL (18.8%), similarly often overestimating (n = 30) and underestimating (n = 32) the actual graft volumes.
Biliary System
In 249 of 250 examined candidates, the biliary tree was clearly visualized to the second and frequently even to the third and fourth level of intrahepatic branches. "Standard" anatomy according to the Couinaud classification (23) was seen in 152 patients (type A: 60.8%; Fig 2). In 97 patients (38.8%), biliary variants were revealed, which included trifurcation at the upper biliary confluence (type B: n = 39, 15.7%), right anterior or posterior sectorial duct draining separately into the common hepatic duct (type C: n = 37, 14.9%), right anterior or posterior sectorial duct joining the left hepatic duct separately (type D: n = 11, 4.4%; Fig 3), or absence of a defined upper biliary confluence with all sectorial ducts joining separately (type E: n = 10, 4.0%). Table 2 summarizes the results concerning the preharvest multi–detector row CT analysis of the biliary system.
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Hepatic Arteries
CT angiograms accurately delineated the arterial supply of both hepatic lobes in all 250 patients. According to the classification by Michel (19), images in 150 patients (60.0%) revealed standard arterial anatomy, with both lobes supplied by single arteries originating from the celiac trunk via the common and proper hepatic artery (type 1; Fig 4a ). In 100 candidates (40.0%), images revealed variants of the hepatic arterial supply, including replacement of the left hepatic artery to the left gastric artery (type 2: n = 10, 4.0%), replacement of the right hepatic artery to the superior mesenteric artery (type 3: n = 21, 8.4%; Fig 5), replacement both of the right hepatic artery to the superior mesenteric artery and of the left hepatic artery to the left gastric artery (type 4: n = 9, 3.6%; Fig 6), presence of an accessory left hepatic artery deriving from the left gastric artery (type 5: n = 40, 16.0%), presence of an accessory right hepatic artery deriving from the superior mesenteric artery (type 6: n = 2, 0.8%), presence both of an accessory right hepatic artery from the superior mesenteric artery and of an accessory left hepatic artery from the left gastric artery (type 7: n = 2, 0.8%), replacement of the right hepatic artery in combination with an accessory left hepatic artery or replacement of the left hepatic artery in combination with an accessory right hepatic artery (type 8: n = 8, 3.2%), and derivation of the proper hepatic artery from the superior mesenteric artery (type 9: n = 4, 1.6%).
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Portal Veins
In 248 of 250 examined candidates, the portal venous system was clearly visualized. "Standard" anatomy according to the classification of Akgul et al (21), including bifurcation of the main portal vein into left and right portal veins, was seen in 195 patients (type A: 78.6%; Fig 7). In 53 subjects (21.4%), anatomic variants were revealed, which included trifurcation of the main portal vein (type B: n = 38, 15.3%), right anterior portal vein deriving from the left portal vein (type C: n = 10, 4.0%; Fig 8), left portal vein originating from the right anterior portal vein (type D: n = 3, 1.2%), and right anterior portal vein deriving from the main portal vein (type E: n = 2, 0.8%). Table 4 summarizes the results concerning the preharvest multi–detector row CT analysis of the portal venous system.
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Hepatic Veins
In 248 of 250 examined candidates, the hepatic venous system was accurately demonstrated. According to the classification of the right hepatic drainage pattern by Nakamura and Tsuzuki (22), type 1 drainage was seen in 140 patients (56.5%), which included a large right hepatic vein draining an extensive area of the right lateral sector and part of the right paramedian sector (Fig 9). In 71 candidates (28.6%), type 2 hepatic venous drainage was present, which included at least one thick inferior right hepatic vein draining directly into the inferior vena cava (Fig 10). In 37 subjects (14.9%), findings at CT angiography revealed type 3 drainage, which included right lobe drainage allocated to a short right hepatic vein, a large-sized middle hepatic vein, and an inferior right hepatic vein. Table 5 summarizes the preharvest results concerning the hepatic venous system.
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Coincidental Findings
One candidate suspected of having subclinical kidney malignancy underwent diagnostic laparotomy, which revealed a renal cell carcinoma. In one individual, an agenesis of the left kidney was diagnosed. One candidate had a left ventricular cardiac aneurysm.
Other incidental findings not of direct relevance to the preoperative assessment were as follows: adrenal adenoma (n = 1), adrenal calcification (n = 1), accessory renal arteries (n = 41), splenic cyst (n = 1), pancreatic cyst (n = 1), gastric sliding hernia (n = 1), and bronchiectasis (n = 1).
Postoperative Complications
During the postoperative survey, eight of 62 donors had a complication that required additional imaging or therapeutic intervention: perihepatic hematoma or seroma (n = 2), perihepatic bilioma (n = 2), perihepatic abscess most likely due to superinfection of a hematoma or bilioma (n = 3), and pneumonia (n = 1). Two of the patients with abscesses underwent radiologic drainage, and the third patient underwent repeated laparotomy.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The all-inclusive multi–detector row CT examination was well tolerated by almost 90% of the candidates. Twenty-seven subjects (10.8%) had moderate adverse reactions, which could be successfully antagonized with standard antihistaminic therapy within 20 minutes. This value considerably exceeds the rate of adverse reactions expected for patient collectives examined solely with use of a conventional nonionic and hypo-osmolar contrast agent, which currently is estimated to be approximately 3% (37). Since our outlined CT protocol includes simultaneous administration of both contrast agents, it does not permit us to definitely attribute the symptoms to one of the contrast agents. In previous articles, authors have reported the association of biliary contrast agents with considerable side effects ranging from mild and self-resolving symptoms (sensation of warmth, unpleasant taste, nausea, vomiting, and erythema; approximately 2% of patients) to moderate and severe systemic adverse reactions up to shock syndrome and death (approximately 0.01% of patients) (38,39); it appears most likely that the biliary contrast agents are responsible for the observed symptoms in our study group as well.
Accurate assessment of the biliary anatomy is known to have a major effect on the postoperative results. Failure to recognize even minor intrahepatic branches crossing the dissection line can result in severe postoperative leaks and other complications (40,41). Even though the preoperative information rarely leads to exclusion of the donation process (26) or a dramatic change of the surgical approach, awareness of biliary variations may prompt thorough exploration to localize the critical structures.
The diagnostic alternatives for analysis of the biliary tree involve considerable drawbacks. Standard MR cholangiopancreatography techniques based on T2-weighted MR images have been shown to be frequently insufficient to depict the normal intrahepatic bile ducts beyond the hepatic bifurcation (42). Even though recent MR cholangiopancreatography studies involving the use of dedicated biliary MR contrast agents (eg, mangafodipir trisodium) show promising results (43), the value of this technique for the evaluation of liver donors remains controversially discussed. Recently, Yeh et al (44) performed a comparison of contrast-enhanced CT and MR cholangiography in potential liver donors and confirmed a substantially better visualization of the biliary tract with CT. Endoscopic retrograde cholangiopancreatography represents an invasive technique and is associated with a considerable number of complications (eg, iatrogenic pancreatitis), thus potentially subjecting the voluntary donors to a higher risk than with CT cholangiography. Although biliary variants can be readily depicted by means of intraoperative cholangiography (24,45), this procedure results in time delays and does not permit the surgeon to freely adjust the surgical strategy.
In our study, contrast-enhanced CT cholangiograms displayed the biliary tree at least up to the second, and more often up to third and fourth, intrahepatic branches in 99.6% of all candidates. The fact that only 152 (61.0%) of 249 useable biliary studies revealed standard biliary anatomy confirms previous reports (23,46–48) and also serves as an indication of the importance of preoperative cholangiography in general. The substantial concordance of preoperative and intraoperative findings achieved in our study has been described in previous reports demonstrating complete agreement between CT cholangiography and endoscopic retrograde cholangiopancreatography (38,49). However, the fact that the biliary anatomy was definitely misclassified in four candidates in our study demonstrates that this technique does not protect against potential misinterpretation, although the number was very limited.
The complex vascular anatomy of the liver and the high prevalence of vascular variants reinforce the need for accurate preoperative vascular imaging.
In our study, multi–detector row CT angiography allowed excellent delineation of the hepatic arteries up to the small intrahepatic branches in all 250 evaluated candidates. The hereby determined anatomic pattern was intraoperatively confirmed in 57 (92%) of the 62 donors; in the other five subjects, either a right or a left hepatic branch was missed. All initially missed branches could be retrospectively detected on the CT images, which suggests that the reviewers' sensitization for the presence of hepatic arterial variants might be a more limiting factor than the achievable image quality. This is supported by results in the respective literature demonstrating complete agreement between CT angiography and digital subtraction angiography (50).
The importance of sufficient display of the hepatic venous system is evident, since the liver outflow represents a crucial predictor for both the graft and the remnant liver function. Preharvest imaging thus has to depict larger venous structures that will need to be transected or should be preserved. One of the critical issues is the reliable identification of an accessory inferior right hepatic vein. Preoperatively, such were detected in almost 29% of the candidates in our study group. Another five findings were intraoperatively identified as false-negative; four of these false-negative findings could be retrospectively recognized as well. Altogether, the rate of type 2 variants noninvasively assessed ranges slightly below the pattern described by Nakamura and Tsuzuki (22), which was based on the analysis of plastic casts of 83 livers. The fact that one intraoperatively objectified branch was persistently missed on the CT images reflects that adequate contrast material enhancement is crucial.
By leveling the difference between perfused graft volume and perfused graft weight by a 1.15 conversion factor, the match between the predicted and the objective values was very close. This way of proceeding represents a compromise between the recommendations of Lemke et al (36) to use a reciprocal 0.75 correction factor, and the established methods of one-to-one correlations. The latter approach is supported by results of several recent studies that evidence an almost excellent one-to-one correlation (34,51). In our experience, however, such a procedure leads to a general tendency to overestimate the effective mass of the nonperfused graft.
A potential limitation of the presented multi–detector row CT protocol relates to the fact that it does not include a real precontrast scan; hence, a fatty infiltration of the liver might be masked by an uptake of the initially administered biliary contrast agent. This is important, since distinctive steatosis may increase the incidence of ischemia–reperfusion injury and primary nonfunction in the recipients. This potential limitation is considered acceptable, since the value of cross-sectional imaging for this indication is still a matter of controversy (29,52–54). Therefore the use of liver biopsy remains the reference standard in determining the degree of steatosis and, to our knowledge, still represents a mandatory step in most preharvest evaluation protocols (also at the authors' institution of University Hospital Essen).
Another considerable limitation of the outlined 3D multi–detector row CT evaluation is the associated exposure to ionizing radiation. The effective dose is estimated to range between 15 and 20 mSv. This compares with 7–12 mSv for a standard CT scan of the abdomen, with approximately 0.2 mSv for a chest radiograph in two projections, and with approximately 2.4 mSv of natural radiation exposure per year. Another limitation of the CT protocol is the necessity to administer considerable volumes of potentially nephrotoxic iodinated contrast agents. Therefore, confirmation of normal renal function prior to the CT examination is mandatory.
Similarly comprehensive approaches based on MR imaging have recently been proposed (42,55–57). While MR cholangiography has been shown to be accurate regarding the detection of intra- or extrahepatic ductal dilatation (58,59), the spatial resolution is frequently insufficient to depict the normal biliary system beyond the hepatic bifurcation. This represents a considerable drawback in the preoperative assessment of potential liver donors.
In conclusion, the outlined three-phase, dual-enhancement multi–detector row CT protocol represents an all-inclusive approach to evaluate potential living liver donors. This might reduce the need for multimodality evaluation protocols to a minimum. At University Hospital Essen, this protocol currently represents the standard procedure and almost completely eliminates the need for further examinations to determine the candidate's anatomy. Critical issues remain the inherent radiation exposure and the necessity to administer large volumes of potentially nephrotoxic contrast agents, accompanied by a considerable risk of adverse reactions. It is therefore an ethical obligation to fully inform the subjects and to perform the examination with the highest possible level of care.
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FOOTNOTES |
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Abbreviations: 3D = three-dimensional
Authors stated no financial relationship to disclose.
See also the commentary by Gridelli following this article.
Author contributions: Guarantors of integrity of entire study, T.S., A.R., S.G.R.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, T.S., A.R., S.G.R.; clinical studies, all authors; statistical analysis, T.S., A.R., S.G.R.; and manuscript editing, T.S., J.F.D., S.G.R.
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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