Simplicity, voxels, and finding the signal in the noise
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Simplicity, Voxels, and Finding the Signal in the Noise The purpose of being in an academic center is not only to do the work, but also to change how the work is done. The article by U-King-Im and colleagues does just that by contributing to our knowledge of how to cost-effectively select patients for carotid endarter- ectomy. 1 The purpose of carotid intervention and im- aging is to reduce the risk of stroke. The North Amer- ican Symptomatic Carotid Endarterectomy Trial (NASCET), European Carotid Surgery Trial (ECST), and Asymptomatic Carotid Stenosis Study (ACSS) 2–4 justified the risk/benefit ratio of carotid endarterectomy by stroke risk reduction in specific groups. The pa- tients in those studies had their stenoses evaluated by digital subtraction angiography (DSA). Great emphasis is placed on the risk of catheter angiography in these three published articles about noninvasive imaging. This has become ingrained in physician training so that cerebral angiography has become an unfashionable and dangerous test. A total of four disabling strokes oc- curred after catheter angiography in the NASCET study. 2 Despite advances in noninvasive imaging meth- ods, overreading persists usually in the region of the 50% angiographic threshold for stenosis. Carotid near occlusion was observed in 7.6% of NASCET angio- grams and is commonly misread on noninvasive studies as total occlusion. Together, overreading and misread- ing account for approximately 15% of images resulting in either unnecessary carotid endarterectomy (CEA) or denial of CEA. The patient then faces a 2% risk of disabling stroke from carotid endarterectomy in the NASCET study, 20 times greater than the risk of dis- abling stroke from DSA (0.1%). 5 Real-world post-CEA and carotid stenting stroke risk is dependent on sur- geon volume and experience, with stroke rates ranging from 2 to 8%; therefore, in fact, the postintervention stroke risk range is 20 to 80 times higher than that of a catheter angiogram. The cost-effectiveness of nonin- vasive imaging over the catheter angiography can easily be lost with the stroke rehabilitation and social costs of one patient who has had a bad outcome from an un- necessary endarterectomy or carotid stent. Approximately 80% of carotid endarterectomy pa- tients in the United States are estimated to have un- dergone the procedure based on ultrasound alone. This is usually performed in a vascular laboratory run by a vascular surgeon. How is it acceptable to use a tech- nique that overestimates the severity of a stenosis and applies to it the data from a completely different test (DSA). Why is this phase shift tolerated? The same is- sue of overestimation applies to magnetic resonance an- giography (MRA) and computed tomography angiog- raphy (CTA). Using two modalities that provide concordant overestimation simply means that two non- invasive methods are equally inaccurate. The work flow of a radiology department or vascular imaging laboratory has an important impact on qual- ity, sensitivity, and specificity. Ultrasound is remark- ably operator dependent, and, in the United States, most ultrasounds are performed by a technologist and secondarily remotely reviewed by a radiologist perhaps across a PACS system or by a vascular surgeon. These physicians usually review snapshots of the overall study and rarely if ever perform the study themselves. This is as meaningful as reading a book review instead of read- ing the book itself. In Europe, ultrasounds are primar- ily performed by physicians, whose methods are based on medical training and personal examination, rather than technologists. In the United States, reconstructions of CTA or MRA are performed by technologists or even out- sourced to countries such as India. This is primarily because the reimbursement is $50 per three- dimensional reconstruction so it is not cost-effective to use physicians’ time and effort for those studies. All of this challenges the relevance of noninvasive imaging studies performed in centers of excellence by people with particular research interests in a particular modal- ity and the applicability of that data to real-world ex- perience. DSA catheter angiography is well reimbursed and physicians and their teams will spend 2 or 3 hours preparing for, performing, and interpreting one partic- ular study for one particular patient. When we apply the same level of focus to noninvasive carotid imaging that we apply to catheter angiography, then we will be able to extract from the safer and noninvasive methods their full and excellent potential. Intrinsic to articles on noninvasive procedures is the assumption that all x-ray machinery is equal. 2–4 This is simply not true. We know that all cars are not equal, that all planes are not equal, and that all athletes are not equal; similarly in x-ray equipment CT scanners and magnetic resonance imaging (MRI) machines vary enormously in their quality. These 1 to 2 million dol- lar machines tend to be used for 5 to 10 years before replacement. The presence of a flow void on MRI has repeatedly been interpreted as indicating a hemody- EDITORIAL © 2005 American Neurological Association 493 Published by Wiley-Liss, Inc., through Wiley Subscription Services
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Transcript of Simplicity, voxels, and finding the signal in the noise
Simplicity, Voxels, and Findingthe Signal in the Noise
The purpose of being in an academic center is not onlyto do the work, but also to change how the work isdone. The article by U-King-Im and colleagues doesjust that by contributing to our knowledge of how tocost-effectively select patients for carotid endarter-ectomy.1 The purpose of carotid intervention and im-aging is to reduce the risk of stroke. The North Amer-ican Symptomatic Carotid Endarterectomy Trial(NASCET), European Carotid Surgery Trial (ECST),and Asymptomatic Carotid Stenosis Study (ACSS)2–4
justified the risk/benefit ratio of carotid endarterectomyby stroke risk reduction in specific groups. The pa-tients in those studies had their stenoses evaluated bydigital subtraction angiography (DSA). Great emphasisis placed on the risk of catheter angiography in thesethree published articles about noninvasive imaging.This has become ingrained in physician training so thatcerebral angiography has become an unfashionable anddangerous test. A total of four disabling strokes oc-curred after catheter angiography in the NASCETstudy.2 Despite advances in noninvasive imaging meth-ods, overreading persists usually in the region of the50% angiographic threshold for stenosis. Carotid nearocclusion was observed in 7.6% of NASCET angio-grams and is commonly misread on noninvasive studiesas total occlusion. Together, overreading and misread-ing account for approximately 15% of images resultingin either unnecessary carotid endarterectomy (CEA) ordenial of CEA. The patient then faces a 2% risk ofdisabling stroke from carotid endarterectomy in theNASCET study, 20 times greater than the risk of dis-abling stroke from DSA (0.1%).5 Real-world post-CEAand carotid stenting stroke risk is dependent on sur-geon volume and experience, with stroke rates rangingfrom 2 to 8%; therefore, in fact, the postinterventionstroke risk range is 20 to 80 times higher than that ofa catheter angiogram. The cost-effectiveness of nonin-vasive imaging over the catheter angiography can easilybe lost with the stroke rehabilitation and social costs ofone patient who has had a bad outcome from an un-necessary endarterectomy or carotid stent.
Approximately 80% of carotid endarterectomy pa-tients in the United States are estimated to have un-dergone the procedure based on ultrasound alone. Thisis usually performed in a vascular laboratory run by avascular surgeon. How is it acceptable to use a tech-nique that overestimates the severity of a stenosis andapplies to it the data from a completely different test
(DSA). Why is this phase shift tolerated? The same is-sue of overestimation applies to magnetic resonance an-giography (MRA) and computed tomography angiog-raphy (CTA). Using two modalities that provideconcordant overestimation simply means that two non-invasive methods are equally inaccurate.
The work flow of a radiology department or vascularimaging laboratory has an important impact on qual-ity, sensitivity, and specificity. Ultrasound is remark-ably operator dependent, and, in the United States,most ultrasounds are performed by a technologist andsecondarily remotely reviewed by a radiologist perhapsacross a PACS system or by a vascular surgeon. Thesephysicians usually review snapshots of the overall studyand rarely if ever perform the study themselves. This isas meaningful as reading a book review instead of read-ing the book itself. In Europe, ultrasounds are primar-ily performed by physicians, whose methods are basedon medical training and personal examination, ratherthan technologists.
In the United States, reconstructions of CTA orMRA are performed by technologists or even out-sourced to countries such as India. This is primarilybecause the reimbursement is $50 per three-dimensional reconstruction so it is not cost-effective touse physicians’ time and effort for those studies. All ofthis challenges the relevance of noninvasive imagingstudies performed in centers of excellence by peoplewith particular research interests in a particular modal-ity and the applicability of that data to real-world ex-perience. DSA catheter angiography is well reimbursedand physicians and their teams will spend 2 or 3 hourspreparing for, performing, and interpreting one partic-ular study for one particular patient. When we applythe same level of focus to noninvasive carotid imagingthat we apply to catheter angiography, then we will beable to extract from the safer and noninvasive methodstheir full and excellent potential.
Intrinsic to articles on noninvasive procedures is theassumption that all x-ray machinery is equal.2–4 This issimply not true. We know that all cars are not equal,that all planes are not equal, and that all athletes arenot equal; similarly in x-ray equipment CT scannersand magnetic resonance imaging (MRI) machines varyenormously in their quality. These 1 to 2 million dol-lar machines tend to be used for 5 to 10 years beforereplacement. The presence of a flow void on MRI hasrepeatedly been interpreted as indicating a hemody-
EDITORIAL
© 2005 American Neurological Association 493Published by Wiley-Liss, Inc., through Wiley Subscription Services
namically significant stenosis worthy of an endarterec-tomy.6 Presence of a flow void on time-of-flight MRAcorresponds to stenosis in a range as wide as 36 to100% according to NASCET criteria in a study pub-lished by Nederkorn and colleagues.6 Flow voids canbe artifactually produced by heavily calcified plaques orcarotid stents that preclude maximum intensity projec-tion (MIP) evaluation on MRA (or CTA) and can leadto overestimation of stenosis in CT. MRA is notori-ously susceptible to motion artifact because of its pro-longed imaging time. The point at which a flow void isgenerated in a stenosis is also dependent on magnetfield strength. A 0.22-tesla Siemens (South Iselin, NJ)open MRI will show a flow void in a stenosis at alower percentage of stenosis than a 3.0-tesla SiemensMRI. The age of the MRI, the gradients, the pulsesequence parameters, and the skill of the MR technol-ogist are all factors too.
A voxel is a volume of data, and the smaller andmore uniform it is the more accurate it represents thetissue it was created from. The Siemens DSA machinein U-King-Im et al., article had 1,024 � 1,024 reso-lution with a 0.32 � 0.32mm voxel. This is an isotro-pic or perfect cube of data. Their MRI is not identi-fied, but they state that it is nonisotropic to achieve thecoverage they need to image from the arch to the head.They report a voxel of 0.6 � 0.8mm. Their resolutionwas probably approximately 256 � 256. The analogysprings to mind the pixilated image from a Nokia tele-phone camera running at 0.3 megapixels (MRI) versusa 6-megapixel Nikon (DSA). Hence, we have the sys-tematic MRI overestimation of stenosis. In any imag-ing modality, no two manufactures are the same. A 16-slice Toshiba Multidetector CT scanner (MDCT)produces a 0.325mm isotropic voxel, whereas a GE 16-slice MDCT produces a 0.625 isotropic voxel. This is50% less data acquired per study. All this affects qual-ity before the image even gets to the radiologist. Thereconstructed images look the same, but this is causedby reconstruction programs that smooth the gaps be-tween images. These smoothing algorithms guess whatwent between slices, resulting in loss of data and accu-racy. Loss of data results in overestimation of stenosis.Each manufacturer uses a different three-dimensionalworkstation, and fundamentally there is a relationshipto the ease of use, the speed of image reconstruction,and the depth of detail being presented. We must nowtherefore include the knowledge that not all three-dimensional workstations are equal either.
CMS recently approved reimbursement for carotidstenting of patients with symptomatic carotid stenosesgreater than 70%. This will lead to a significant in-crease in stent implantation. The follow-up imaging of
a patient with a stent by noninvasive technology isproblematic. All carotid stents have MR, CT, and ul-trasound artifacts that prevent accuracy in stent imag-ing to detect neo intimal hyperplasia and in stent re-stenosis. Cobalt steel wallstents (Boston Scientific,Watertown, MA) create a bigger flow void than Niti-nol Smart stents (Cordis, Miami, FL; Johnson andJohnson, Warren, NJ). Ultrasound suffers from in-creased reflection from stent metal. CT suffers frombeam hardening artifact, which varies slightly frommanufacturer to manufacturer. Selective DSA catheterangiography will continue to be necessary in this pa-tient population until effort is placed on the postim-plantation imaging characteristics of stents.
Many relatively unskilled newcomers to the field ofangiography are looking to increase their case series ofcarotid angiography so that they can meet hospital cre-dentialing committee criteria to perform carotid stent-ing. Most of this is done on low-cost portable C armsin operating rooms before carotid stenting. More pa-tients will be exposed to less experienced angiogra-phers, and the carotid angiogram stroke rate will in-crease. The national reporting of personal physiciancerebral angiography complication rates is needed sothat patients can give truly informed consent. The es-tablishment of well thought out criteria for the appro-priate performance of carotid angiography is timely.
Kieran Murphy, MD, FRCPCJohn Hopkins UniversityBaltimore, MD
References1. U-King-Im JMU, Hollingworth W, Trivedi RA, et al. Cost-
effectiveness of diagnostic strategies prior to carotid endarterec-tomy. Ann Neurol 2005;58:506–515.
2. Barnett HJ, Taylor DW, Liaszi WM, et al. Benefits of carotidendarterectomy in patients with symptomatic moderate or severestenosis. North American Symptomatic Carotid EndarterectomyTrial Collaborators. N Engl J Med 1998;339:1415–1425.
3. Randomized trial of endarterectomy for recently symptomatic ca-rotid stenosis: final results of the MRC European Carotid Sur-gery Trial (ECST). Lancet 1998;351:1379–1387.
4. Endarterectomy for asymptomatic carotid artery stenosis. Execu-tive committee for the Asymptomatic Carotid Stenosis Study.JAMA 1995;273:1421–1428.
5. Barnett HJ, Meldrum HE, Eliasziw M; North American Symp-tomatic Carotid Endarterectomy Trial (NASCET) Collaborators.The appropriate use of carotid endarterectomy. Can Med Assoc J2002;166:1169–1179.
6. Nederkoorn PJ, van der Graaf Y, Eikelboom BC, et al. Time offlight MR angiography of the carotid stenosis: does a flow voidrepresent severe stenosis? Am J Neuroradiol 2002;23:1779–1784.
DOI: 10/1002.ana.20674
494 Annals of Neurology Vol 58 No 4 October 2005
