Keywords: angiography, CTA, cerebral aneurysm, diagnostic yield, subarachnoid haemorrhage.

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1 Original research Volume 58 (1) 2011 A retrospective review of multi-slice CT and DSA reports in patients with non-traumatic subarachnoid haemorrhage and the resultant diagnostic yield of aneurysms E Marshall B Rad Med Imaging (Hon) Grad Dip of Advanced Radiographic Practice B Erskine B App Science (Medical Radiations) Grad Cert of Advanced Radiographic Practice Abstract Purpose: To examine the diagnostic yield differences between computed tomography angiography (CTA) and digital subtraction angiography (DSA) at The Alfred Hospital, Australia in order to justify patient management that results in all subarachnoid haemorrhage (SAH) patients receiving a 4 vessel cerebral angiogram as part of their investigations despite findings on CTA. Methods: The retrospective study of radiology reports in cases of acute non traumatic SAH in which both CTA and DSA had been performed was conducted in July 2006 to December Results: Sixty-three patients over two years were included in our study. Twenty (32%) of these patients had no aneurysm identified on CTA or DSA. A total of 68 aneurysms were found in 40 patients. Twelve (30%) of these patients had aneurysms that were only identified on DSA and not on CTA at the time of initial reporting. Three (5%) patients had false positive CTs. While our positive predictive value of CTA approached near 100%, the negative predictive value was found to be less than 70% with an overall diagnostic accuracy of our CTA reports to be 76%. Eighty one percent of the undiagnosed aneurysms on CTA were less than or equal to 3 mm in size. Conclusion: These findings demonstrate the need for a CTA to be used in combination with a formal 4 vessel subtraction angiogram in every case presenting with a SAH despite the findings of the CTA. Keywords: angiography, CTA, cerebral aneurysm, diagnostic yield, subarachnoid haemorrhage. The Alfred Hospital Department of Radiology Prahran Victoria 3181 Australia Correspondence to e.marshall@alfred.org.au 4 The Radiographer 2011 Introduction Although there are several causes of non traumatic subarachnoid haemorrhage (SAH), aneurysms contribute to 85% 1 and hold a high morbidity and mortality rate. The fatality rate including pre-hospital deaths is quoted as high as 80%. 2 For patients that survive the initial haemorrhage, there is increased rate of re-bleeding if the aneurysm is not treated. This is up to 2 4% for the first 24 hours, 15 20% within the first two weeks and up to 50% in the first six months. 1 This contributes to the high mortality rate, and hence stresses the importance of quick and accurate diagnosis of cause of SAH. Saccular aneurysms, both ruptured and unruptured, appear in patients from 2 6% 2 of the population across the world. They grow unpredictably and even small aneurysms possess a risk of rupture. Our study determines the diagnostic accuracy of our 64 slice computed tomography angiography (CTA) reports with respect to diagnostic yield of aneurysms in comparison to our digital subtraction angiography (DSA) including three-dimensional (3D) DSA. Materials and methods Ethics approval was gained through The Alfred Hospital s research organisation as a low risk study on 27th February 2008, project number: 36/08. A total of 63 patients from July 2006 to December 2008 were included in the study. Thirty-four females and 29 males ranging in age from 18 to 84 years of age formed the study group. These patients all underwent a 64 slice CTA with a 3 vessel (single vertebral injection) or 4 vessel (bilateral vertebral injection) DSA following non-traumatic SAH. Cases with discordant CTA and DSA findings were reviewed in more detail. Our retrospective review of reports denotes that radiologists were not blinded to the results of the CTA when reporting the DSA. It was our intention to represent the typical work up in the clinical setting to truthfully assess the diagnostic accuracy of our CTA reporting of aneurysms later confirmed on DSA. CTA protocol The CT scanner in use for the duration of this study was the GE Lightspeed VCT 64. Technical factors are identified in Table 1. A retrospective reconstruction of 12 cm display field of view (DFOV) covers the circle of Willis and is used to produce the 4 mm thickness maximum intensity projection (MIP) reformats in axial, sagittal and coronal planes as well as a 3D volume rendered (VR) model. The reporting radiologist has access to the MIPS and VR model archived on our picture archiving communication system (PACS) as well as the raw data on the workstation for further scrutiny. DSA technique For the duration of the study, the angiography unit in use was the GE LCV+ Advantx system. This had a 3D rotation package linked to a GE Advantage Workstation (Version 3.1, GE Fairfield CT, USA). Our standard imaging protocol was to examine both

2 Table 1: Technical factors for CT circle of Willis (COW) scan performed on GE Lightspeed VCT 64. Slice thickness 64 x mm Rotation time 0.5 seconds Table speed mm per rotation Reconstruction interval mm Pitch Scan field of view (SFOV) 25 cm kvp 120kVp Noise index 5 Maximum ma 330 ma Table 2: Technical factors for 2D cerebral DSA acquisitions performed on the GE LCV+ Advantx system. FOV 22 cm or 32 cm Dose Rate 250uR to 500uR per frame Frame Rate Variable: 2.1 frames per second to 0.5 frames per second internal carotid arteries (ICA) and the vertebrobasilar system intracranialy in a posterior-anterior (PA) and lateral projection using the technical factors listed in Table 2. If no aneurysm was seen on the PA and Lateral ICA projections, a transorbital oblique projection was performed to demonstrate the middle cerebral artery (MCA) bifurcation / trifurcation and also provide a second look at the anterior communicating (ACOM) artery region. If an aneurysm was suspected or seen on any of the two-dimensional (2D) projections then a 3D DSA dual spin was performed to produce a 3D volume rendered model as per the technical factors in Table 3. Representative images of the DSA were archived to PACS. These included early and late arterial, capillary phase and early and late venous phases. Volume rendered 3D rotational images every 10 degrees were sent to PACS about the horizontal and vertical axis along with additional 3D images that best demonstrate the aneurysm and its relationship to parent vessels with measurements of neck and maximum dome dimensions. At the time of acquisition, the images are individually assessed at the modality, before completing the examination to ensure complete evaluation of the vasculature is provided. Contrast considerations DSA used a standard approach to contrast volume and rate, and is varied according to size of vasculature. For each selective vessel (ICA and vertebral artery) a 6 ml at 3 ml/s is given for each projection undertaken. The 3D rotational acquisition required for assessment of aneurysm uses 18 ml at 3 ml/sec. An average patient who has one 3D and 4 vessels imaged as per standard protocol would receive 72 ml of Ultravist 300 (Bayer Healthcare Pharmaceuticals, Montville NJ). The actual amounts injected in our study based on the sequences performed was calculated as an average of 80 ml. This volume did not include the volume required for intervention, only diagnostic and work up for interventions CTA in our department used 80 ml of Ultravist 370 injected at 4 ml/sec peripherally with a 40 ml saline chase. Results Of the 63 patients included in this study, 20 (32%) patients had no aneurysm identified on CTA or DSA. Three (5%) patients had false positive Table 3: Technical factors for 3D dual spin DSA acquisition performed on the GE LCV+ Advantx system with the GE Advantage Workstation (Version 3.1). Spin time 6 seconds Spin speed 40 degrees per second Total rotation arc 200 degrees Frame Rate 8.8 frames per second Field of View (FOV) 16 cm Dose Rate 500uR per frame Focal spot 0.6 mm Matrix 512 x 512 Effective voxel size 0.2 mm CTAs with three aneurysms that were later confirmed as false on DSA. Twelve (19%) patients had aneurysms that were only identified on DSA and not on CTA at the time of initial reporting. Two of these patients had their CTA reports modified/revised after DSA confirmed the presence of aneurysms that were in fact subtly visible on CTA in the first place. One additional patient had an MCA aneurysm that was not reported on the CTA, but was however clipped at the time of surgery for clipping of an ACOM aneurysm. Of the 12 patients with aneurysms only identified on DSA, 10 patients had multiple aneurysms with three of these 10 patients having two or more additional aneurysms diagnosed only on DSA. A total of 68 aneurysms were found in 40 patients. Eighteen patients had multiple aneurysms. Sixteen aneurysms were undiagnosed on the initial CTA. The distribution of aneurysms including those that were undiagnosed on CTA are shown in Table 4. Fifteen of 63 patients (24%) had incomplete / inaccurate diagnosis made on CT alone (12 false negative (19%), three false positive (5%)). Sixteen of 68 aneurysms (24%) were undiagnosed on CT. Two primary aneurysms (assumed cause for SAH) were not identified initially on the CTA. One was later treated endovascularly and the other was clipped neurosurgically. Of the 16 aneurysms that were missed 13 (81%) were 3 mm, one was 3.5 mm, one was 3.6 mm. Management of these missed aneurysms were as follows: Two MCA aneurysms were clipped One superior cerebellar artery (SCA) aneurysm was coiled successfully Unsuccessful attempts were made to coil 1 x MCA aneurysm and 1x anterior choroidal artery (AChA) aneurysm following which these lesions will be monitored for interval growth. All others were to be monitored for interval growth with DSA and magnetic resonance angiography (MRA). Of the 20 patients who had no identifiable aneurysm, there was either an alternative diagnosis for clinical presentation or there was no cause identified for SAH. These patients were considered negative for the purpose of statistical calculations despite their pathologies. Additional diagnostic examinations were employed to identify any cause for SAH in these patients. They underwent further DSA or magnetic resonance imaging (MRI) or both. Two patients had arterio-venous malformations (AVMs) that were considered the cause for their SAH. One of these was only identified on DSA. Six patients demonstrated bleeding patterns consistent with perimesencephalic bleeds with no other cause identified. One patient who presented with positive lumbar puncture for SAH demonstrated abnormal draining veins, but no identifiable cause for SAH. One patient demonstrated atherosclerotic disease appreciated only on the DSA but with no identifiable cause for SAH The Radiographer

3 Table 4: Distribution of aneurysms including undiagnosed aneurysms on CTA. Anatomical Location Number of aneurysms Number of undiagnosed aneurysms on CTA % of undiagnosed aneurysms at given anatomical location % of undiagnosed aneurysms Maximum dome size of undiagnosed aneurysms as confirmed on DSA Anterior Communicating Artery 11 Middle Cerebral Artery % * 25% 2.9 mm, 2.7 mm, 2.3 mm clipped* Ophthalmic Artery % 6% 3.6 mm Posterior Communicating Artery 8 Anterior Choroidal Artery % 13% 3 mm, 2 mm Pericolosal Artery % 6% 2.5 mm Superior Cerebellar Artery % 6% 3 mm Internal Carotid Artery % 38% 3.5 mm, 3 mm, 2.8 mm, 1.5 mm, 1 mm, < 1mm Basilar Artery % 6% 1 mm Vertebral Artery 2 Posterior Inferior Cerebellar Artery 3 Posterior Cerebral Artery 3 Total % *4 MCA aneurysms were missed on CTA. 3 of these were amended after review of the DSA while the remaining 1 MCA aneurysm was clipped by neurosurgery despite not being documented on the CTA report. One angioma was diagnosed on DSA alone. This is questionable as to whether this could be the cause for the minimal SAH diagnosed on an external MRI. The remaining 9 patients had no identifiable cause for SAH on CT, DSA or MRI and no additional pathology Discussion Our primary aim was to demonstrate that conventional DSA was still a necessary diagnostic tool for identifying aneurysms in the setting of acute non traumatic SAH. We established that while multi-slice CT is useful for initial investigations in SAH in our clinical setting, full diagnostic yield of aneurysms could not be achieved without the use of DSA including 3D DSA. 3D rotational angiography has been previously determined to be accurate for aneurysm detection and assessment. 3 Bridcut, et al. (2002) conducted studies to assess the degree of geometric distortion in a 3D image created by a rotating C arm by determining the accuracy of small ball bearing measurements. 3 Their resultant error was from -1.0% to +2.3%. 3 This is considered clinically negligible, enabling subjective assessments to be made with confidence to aid intervention. At our institution, we have long been using this degree of confidence in planning and conducting clipping and coiling. A review of previous literature indicates that 64 slice CTA on a patient basis has a sensitivity of between 77 and 98 with specificity between 90 and 100 and reported negative predictive values of between 70 and , 5,6,7 Our results are in keeping with this, with a negative predictive value below 70% owing to the high number of false negative CTAs. Of particular interest in this false negative group is the number of missed primary aneurysms. Two (12.5%) of the 16 missed aneurysms were primary aneurysms, therefore, CTA reporting missed two (5%) of the 40 primary aneurysms. As the risk of death from re-rupture is far higher than the risk of death from cerebral angiography, 2 digital subtraction angiography should be considered in the patients best interest to be performed in conjunction with a CTA. 6 The Radiographer 2011 DSA has a reported risk of neurological complication in about 1 to 2.5% of patients while permanent risk of neurological complication is quoted at 0.1 to 0.5% with elderly patients more likely to have complications. 5 Only the dominant vertebral artery is required for selection provided that the contralateral posterior inferior cerebellar artery (PICA) is visualised on these images in order to reduce procedural time and hence reduce complications. 6 There is also a 1% non neurological risk associated with arterial puncture and catheter manipulation. 7 While it is easy to argue that CTA has advantages over angiography for detection of aneurysms, due to its non-invasiveness and quick turnaround times, the disadvantages include the lack of detection of smaller vessel abnormalities. Our 3D LCV+ voxel size is 0.2 mm for a 16 cm FOV (standard 3D imaging) while the voxel size of our CT is mm. Technical factors, such as spatial resolution are considered the main cause for aneurysm misdiagnosis on CTA. The comparable voxel size indicates that the sensitivity for detection of aneurysms is going to be greater on 3D DSA compared to CTA. Our study again demonstrates the inability to visualise small vessels such as the posterior communicating artery (PCOM), pericallosal and ophthalmic arteries on the CTA. Other factors that affect the identification of small aneurysms on CTA is the requirement to threshold the vessel to separate it from surrounding structures that may be very similar in Hounsfield units such as bone and venous complexes. This has been found to be true in previous studies in which in particular, the ICA-ophthalmic artery and supraclinoid ICA region is best demonstrated on DSA. 8 Another reason that our CTA aneurysm detection rates are low is that all of our radiologists are involved in the reporting of CTAs in comparison to only specialist radiologists involved in the DSA. Other studies have identified this as a problem and state that neurosurgeons and neuroradiologists with extensive experience with CT volume manipulation and interpretation will improve the diagnostic accuracy and over time with greater experience, the sensitivity for detection of small aneurysms will also improve. 9

4 It has been noted that distal pericallosal and PICA aneurysms can be missed if the CTA FOV is restricted only to the circle of Willis. 10 Care should be taken to ensure an extracranial starting location to cover any extracranial PICA origins and that complete coverage of region of interest is included in the retrospective reconstruction field. Authors have commented that patients suspected of AVM should only have DSA as CTA does not adequately demonstrate the dynamics of flow. 11 This is demonstrated in our results as one patients cause for a bleed was a dural AVM that was not visible on CTA, partially due to the restricted FOV as well as the lack of flow dynamics. Even though AVMs contribute to less than 5% of SAH without intracerebral involvement, saccular aneurysms are found on the feeding vessels in 10 20% of AVM cases and hence should be investigated. 12 Understanding the flow dynamics is important in surgical planning. Even when giant aneurysms are seen on CTA, dynamic information is useful for the surgeon if bypass or sacrifice of a parent vessel is required. This can only be achieved from DSA. Perforating arteries such as the recurrent artery of Heubner or the anterior choroidal artery are usually only seen on DSA, and their visualisation is vital for good surgical outcome. 13 Since multiple aneurysms are found in 10 30% 14 of patients with aneurysms, it is important to look for additional aneurysms even when one has been identified on CT. Controversies still exist about the risk of rupture of unruptured (incidental) aneurysms. A study compiled in 2004 shows that the risk of rupture of a single incidental aneurysm of the small classification was only 0.05% per year. 15 Patients however who have had a SAH from another aneurysm are 11 times more likely to rupture each year. Aneurysms greater than 10 mm or those attributed to the basilar or PCOM arteries were even higher in risk of rupture. 15 MRI is not usually undertaken in the acute setting of SAH as it requires patients to tolerate confined spaces for a length of time. In a cerebrally irritated patient, this is often not possible. MRA therefore is reserved for delayed investigation for SAH, follow up of known aneurysm, or for asymptomatic patients with family history of aneurysms, however it should be mentioned that MRA sensitivity for aneurysms smaller than 3 mm is reported at only 38% 16 MRI/MRA Brain and C spine is used in our department when CT and DSA are negative for a cause for SAH. Due to arterial spasm, a number of cases may be negative and hence warrant a repeat angiogram (usually conventional) days after initial investigation. This may have been the reason why one primary went undiagnosed on CTA and on original DSA. Other causes for negative study could include thrombus at the neck of the aneurysm. This aneurysm was coiled on the subsequent DSA occasion (Figure 1). We believe that our study has accurately identified true detection rates in our institute as the study was performed retrospectively. We did not discriminate between radiology reporters of the CTA or the DSA. The Hawthorne effect is seen in well controlled studies where a contributor knows that their actions will be examined and hence their findings may be influenced. True diagnostic accuracy is determined from a study such as ours that measures the diagnostic value of our CTA reports rather than accuracy of the CT technology. In stating this, there are of course limitations of this study. The number of patients was limited to those only examined using the 64 slice CT scanner and the DSA unit as mentioned. Rather than include those patients imaged on our 16 slice CT scanner or our newer DSA system, we took results that represent a snapshot in time in our department. Our patient cohort included only patients presenting with SAH, and Figure 1: Seventy-one year old female presents with Grade 1 SAH. CTA (left) does not demonstrate the 3mm Right Superior Cerebellar Artery aneurysm diagnosed only on DSA (right). therefore our chance of identifying aneurysms was high as we were actively looking out for a cause of SAH. For this reason, even small irregularities were further examined if seen on the initial CTA. If CTA were used for general screening and incidental small aneurysms were present, we may not have considered them without the presence of SAH. Conclusion Our results demonstrate that our CTA reports had an overall diagnostic accuracy of 76% with 95% of primary aneurysms accurately identified on initial CTA. CTA yielded 76% of all aneurysms later confirmed on DSA. With its better spatial resolution, temporal resolution and ability to visualise the vessel separate from adjoining venous complexes and bone, the diagnostic value of DSA including 3D DSA outweighs the risk associated with this invasive approach and will remain to be used in combination with CTA for all patients presenting with SAH in our department. References 1 Kallmes DF, Layton K, Marx WF, Tong F. Editorial: Death by nondiagnosis: Why emergent CT angiography should not be done for patients with subarachnoid haemorrhage. Am J Neuroradiol 2007; 28: Osborn, AG. Diagnostic cerebral angiography 2nd Edition. USA: Lippincott Williams and Wilkins; Bridcut RR, Winder RJ, Workman A Flynn P. Short Communication: Assessment of distortion in a three-dimensional rotational angiography system. Br J Radiol 2002; 75: Colen T, Wang L, Ghodke B, Cohen W, Hollingworth W, Anzai Y. Effectiveness of MDCT angiography for the detection of intracranial aneurysms in patients with nontraumatic subarachnoid hemorrhage. Am J Roentgenol 2007; 189: Poon TL, Ho WS, Pang KY, Wong CK. Comparison of computerized tomography angiography and digital subtraction angiography in ruptured cerebral aneurysm surgery. Surg Prac 2006; 10: Willinsky RA, Taylor SM, terbrugge K, Farb RI, Tomlinson G, Montanera W. Neurologic complications of cerebral angiography: prospective analysis of 2899 procedures and review of the literature. Radiology 2003; 227: Kouskouras C, Charitanti A, Giavroglou C, Foroglou N, Selviaridis P, Kontopoulos V, Dimitriadis AS. Intracranial aneurysms: Evaluation using CTA nnd MRA. Correlation with DSA and intraoperative findings. Neuroradiology 2004; 46: Teksam M, McKinney A, Cakir B, Truwit CL. Multi-section CT angiography of small cerebral aneurysms: Is the direction of aneurysm important in diagnosis? Eur J Radiol 2005; 53: The Radiographer

5 9 Pechlivanis I, Schmieder K, Scholz M, Konig M, Heuser L, Harders A. Clinical Article: 3 dimensional computed tomographic angiography for use of surgery planning in patients with intracranial aneurysms. Acta Neurochir (Wien) 2005; 147: Westerlann HE, Gravendeel J, Fiore D, Metzemaekers, JDM, Groen RJM, Mooij JJA, Oudkerk M. Multislice CT angiography in the selection of patients with ruptured intracranial aneurysms suitable for clipping or coiling. Neuroradiology 2007; 49: Tomandl BF, Kostner NC, Schempershofe M, Huk WJ, Strauss C, Anker L, Hastreiter P. CT angiography of intracranial aneurysms: A focus on postprocessing. Radiographics 2004; 24: Van Gijn J, Rinkel GJE. Subarachnoid haemorrhage: diagnosis, causes and management. Brain 2001; 124: Amagasaki K, Takeuchi N, Takashi S, Kakizawa T Shimizu T. Current usage of three-dimensional computed tomography angiography for the diagnosis and treatment of ruptured cerebral aneurysms. J Clin Neurosci 2004; 11 (5) Brisman JL, Song JK, Newell DW. Review Article: Medical progress cerebral aneurysms. N Engl J Med 2006; 355 (9) Wiebers DO, Piepgras DG, Meyer FB, Kallmes DF, Meissner I, Atkinson JLD. Link MJ, Brown RD. Pathogenesis, natural history, and treatment of unruptured intracranial aneurysms. Mayo Clin Proc 2004; 79 (12): Keedy A. An overview of intracranial aneurysms. McGill J Med 2006; 9 (2): The Radiographer 2011

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