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Disease evaluation by imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) is an accurate, reproducible, and easily accessible methodology used in pharmaceutical trials.
Disease evaluation by imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) is an accurate, reproducible, and easily accessible methodology used in pharmaceutical trials. The value of imaging tools in the evaluation of response to chemotherapeutic agents and other disease modifying agents has been noted in the literature.1,2
Imaging tools such as CT, MRI, and positron emission tomography (PET) scans have complemented serological markers like CEA (carcino-embryogenic antigen) and PSA (prostate-specific antigen) in disease-response evaluation following chemotherapy in patients with colon carcinoma and prostate carcinoma. Imaging tools give detailed information regarding extent and spread of the cancer when compared to the biochemical markers during disease response evaluation.1
Response evaluation by biochemical markers can give false positive and often inaccurate assessment of tumor response. Imaging modalities such as CT and MRI are advantageous because subtle and early changes in lesion progression can be documented more accurately.
Disease response evaluation by imaging has complemented conventional biochemical markers; there are established protocols like RECIST (Response Evaluation Criteria In Solid Tumors) and WHO (World Health Organization) criteria3,4 for tumor assessment.
Imaging core labs coordinate clinical trials workflow using imaging modalities as the follow-up tool. The images are acquired at various sites all over the world and sent to the imaging core lab, which is analogous to a radiology department. The images received from various sites are either hard-copy films or soft-copy images on magneto-optical disks (MODs) and CDs. The image visualization on computer monitors is analogous to image interpretation using picture archiving and communication systems (PACS) in hospital settings.
Over the past two decades, groups of computer scientists, electronic design engineers, and physicians from universities and industry have achieved an electronic environment for the practice of radiology, with PACS comprising the radiology component of this revolution. It has become evident recently that the efficiencies and cost savings of PACS are more fully realized when they are part of an enterprise-wide electronic medical record. The installation of PACS requires careful planning by all the various stakeholders over many months prior to installation. All of the users must be aware of the initial disruption that will occur as they become familiar with system processes and procedures.
Modern fourth-generation PACS is linked to radiology and hospital information systems.5 PACS consist of electronic acquisition sites-a robust network intelligently managed by a server as well as multiple viewing sites and an archive. The details of how these components are linked and their workflow analysis determines the success of PACS. As PACS evolves over time, components are frequently replaced, and the users must continually learn about new and improved functionalities. The digital medical revolution is rapidly being adopted in many medical centers, improving patient care.
Figure 1. The ideal workflow in a clinical trial with image review at an imaging core lab.
PACS was introduced to clinical practice in the late 1990s. Though initial setup of such a system met with difficulties such as technical incompetence, economic insufficiency, bureaucratic hurdles, and psychological inertia from the clinicians, PACS has become acceptable to the clinicians in general and radiologists in particular.
The PACS workflow itself must be described before we elaborate on its role in network systems. Image acquisition by cassettes using films is replaced by specially designed filmless cassettes, which can be used several times. The basic components of any PACS system include an image acquisition device (such as film cassettes, video frame grabbers, and digital imaging modalities like CT or MRI), an image display station, and database management and image storage devices. Patient images are acquired from the radiography or digital imaging modalities and sent to the PACS workstation. The images are viewed and interpreted there, and the interpretation results are made available to the physicians within the hospital network. An image storage backup system stores images on optical disks and MODs. Images are stored for a time period specified in each hospital's state and local rules.
The images from a hospital without a radiologist can be sent to other hospitals. Modalities including CT, MRI, ultrasound, computed radiography, and nuclear medicine send images to PACS servers in other hospitals directly or via a network gateway. Images can be transmitted on a regional hospital local area network (LAN), then onto high-speed phone circuits to reach the hospital with PACS. They then go onto the network core and PACS servers.
One of the important advantages of PACS is the time saved in comparison with conventional radiology processing. Twair et al. compared a group of 100 radiologic studies performed in a conventional radiology department with an equal number performed in a completely filmless PACS department to assess the difference in the radiologist report turnaround time. There was a statistically significant (P < .00001) decrease in the median imaging-to-dictation time (IDT) of the PACS group (3 hours and 40 minutes) in comparison with the pre-PACS group (25 hours and 19 minutes). This can be attributed to the fact that PACS eliminates all the workload associated with hard-copy films, thus improving the department's efficiency and decreasing the number of lost films.
The problem of nonevaluable films frequently arises in a hospital with PACS facility. In these cases, digital image characteristics like contrast and sharpness can be manipulated for a clear image. Thus, fewer exams are reordered or repeated for technical reasons. The images can be sent from the area of image acquisition to the workstation to the hospital network without the usual film processing steps of developing, fixing, washing, and drying, resulting in a more rapid treatment of patients. This means more patient lives are saved, a better quality of patient management, increased clinician and patient satisfaction, and shorter hospital stays, which in turn may help better patient management.
Patient follow-up is enhanced in a system that makes use of PACS because of better film retrieval rate and more reviewable images. The images can be viewed at more than one location simultaneously, and the interaction between radiologists and referring clinicians can be enhanced. The efficiency of radiologists has been improved since the advent of PACS. The images are viewed and interpreted on the PACS workstation faster than the film viewing process of yesterday.
The main advantage of filmless radiology is the elimination of cost and time involved in developing hard-copy films. But the cost of initial installation and implementation of PACS is a limiting factor, thus obscuring its acceptability in a modest clinical scenario. However, a modest hospital which does not have access to a 24-hour diagnostic radiologist can have access to real-time analysis of images via the Internet for referral purposes. All in all, the only disadvantage of PACS seems to be the inability to hand over images to patients. Of course, physicians can give printouts to patients who request them, or send images over email.
Some retrospective studies conducted several years after the administration of PACS have shown that this system is very cost-effective.7 The creation of PACS has resulted in additional savings and improvements in clinical care. These benefits were made possible, to a large extent, by its high level of integration with medical modalities and the hospital information and transcription systems.
The problems faced by the nonstandardized workflow in a clinical trial core lab are paramount. The images from the study sites are in the hard-copy film format or soft-copy format on CDs or MODs. The hard-copy images have to be shipped directly as films to the imaging core lab. The films undergo a lot of manipulation and handling during this process, and occasionally they are damaged. The shipping charges add further economic burden to the trial. If the site decides to send the images as soft-copy images, they have to be digitized and copied to MODs or CDs and shipped to the imaging core lab. The workflow can easily become disrupted.
The overall cost in time and money of these couriered films can be high, especially compared to a digital infrastructure combined with the Internet. Images can be sent immediately with not only courier savings but also faster image analysis and review by all clinically appropriate individuals. In addition, image analysis on films is extremely limited and often requires redigitization, increasing overall costs. Stories of courier costs consuming thousands of dollars are the norm.
Patient examinations are performed at a clinical site away from the imaging core lab. The images are sent to the imaging core lab as films or MODs. They are received by the clinical research associates (CRAs), who either digitize the hard-copy images or download the soft-copy images to the local network. The images are analyzed by the radiology reviewer, and the results of image analysis are sent to the clinical trial sponsor to integrate with other clinical and biochemical data to judge final disease outcome.
The images are received as hard-copy images on films or soft-copy images on CDs or MODs. The radiology reviewers are blinded to patient information such as name, age, sex, hospital identification, and clinical details. This blinding aims to avoid bias during evaluation. Cases may be single-read (one reviewer per case) or double-read (two radiology reviewers who read independently), according to the clinical trial protocol.
Digital Imaging and Communications in Medicine (DICOM) standards are the international standards for the representation and transmission of all digital medical images.8â10 DICOM, today one of the most popular standards in medicine, was first used for communication of image data between different systems. Actual developments of the standardization enable increasingly more DICOM-based services for the integration of modalities and information systems, such as a radiology information system (RIS).8 DICOM specialists consider DICOM Eye software, which contains many DICOM services, as a definitive reference tool, compatible with nearly all image formats and equipment.
DICOM Eye has myriad applications in healthcare today. The software can help convert images in JPEG, TIFF, GIF, and BMP formats into the DICOM format. It can capture images directly from videos and TWAIN-compatible digitizers.
DICOM-compliant medical imaging equipment (sources, workstations, archive servers, printers) can communicate through a local Internet to import, export or print images. Integration into multimedia reports, publications, case studies, and PC printouts is possible by DICOM Eye's visualization of images on PC (windowing, zoom, multiframe images, etc.) and conversion into Office image formats.
Images manipulated with DICOM Eye can be exported in several ways. DICOM files can be exported to biomedical equipment, through common image formats (BMP, JPEG with a set of quality levels, GIF, PICT, TIFF) or via cut-and-paste applications.
The ideal image-viewing station in a clinical trial should have DICOM-compatible computers capable of displaying the incoming images, making them amenable for radiological evaluation.
In an ideal situation, the DICOM images acquired at various clinical sites are transmitted through the Internet to the imaging core lab. The forms for image transmittal can be sent electronically through the Internet, too. This electronic transmittal of images enhances the workflow by faster and more efficient transmittal and receipt, reducing the cost and potential image damage. The intranet is the local network within the imaging core lab, which helps in the local transmission of images from the DICOM-compatible computer to the individual workstations.
Image acquisition and transmission should be standardized to enhance the workflow in clinical trials. The application of PACS to clinical trials will streamline image interpretation and accelerate the workflow. An ideal PACS system associated with clinical trials should have image transmission in DICOM format, and the ideal workstation in an imaging core lab should have DICOM-compatible computers. This system will be advantageous in avoiding discrepancies in image transmittal and image display. The time and money saved by avoiding the hard-copy film transmittal, potential film damage, and manual digitization may be significant. Imaging core labs, which accelerate the clinical trials, should adhere to standardized image acquisition, transmittal, retrieval, and display.
1. Y. Kitagawa, S. Nishizawa, K. Sano, T. Ogasawara et al., "Prospective Comparison of 18F-FDG PET with Conventional Imaging Modalities (MRI, CT, and 67Ga scintigraphy) in Assessment of Combined Intra-arterial Chemotherapy and Radiotherapy for Head and Neck Carcinoma," J Nucl Med, 44 (2) 198â206 (2003).
2. A.R. Padhani and L. Ollivier, "The RECIST (Response Evaluation Criteria in Solid Tumors) Criteria: Implications for Diagnostic Radiologists," Br J Radiol, 74 (887) 983â986 (2001).
3. S.R. Prasad, S. Saini, J.E. Sumner, P.F. Hahn, D. Sahani, G.W. Boland, "Radiological Measurement of Breast Cancer Metastases to Lung and Liver: Comparison Between WHO (Bidimensional) and RECIST (Unidimensional) Guidelines," J Comput Assist Tomogr, 27 (3) 380â384 (2003).
4. V. Trillet-Lenoir, G. Freyer, P. Kaemmerlen et al., "Assessment of Tumour Response to Chemotherapy for Metastatic Colorectal Cancer: Accuracy of the RECIST Criteria," Br J Radiol, 75 (899) 903â908 (2002).
5. M. Li, D. Wilson, M. Wong, A. Xthona, "The Evolution of Display Technologies in PACS Applications," Comput Med Imaging Graph, 27(2â3)175â184 (2003). G. Gamsu and E. Perez, "Picture Archiving and Communication Systems (PACS)," J Thorac Imaging, 18 (3) 165â168 (2003).
6. A.A. Twair, W.C. Torreggiani, S.M. Mahmud, N. Ramesh, B. Hogan, "Significant Savings in Radiologic Report Turnaround Time After Implementation of a Complete Picture Archiving and Communication System (PACS)," J Digit Imaging, 13 (4) 175â177 (2000).
7. E.L. Siegel and B.I. Reiner, "Filmless Radiology at the Baltimore VA Medical Center: A 9 Year Retrospective," Comput Med Imaging Graph, 27 (2â3) 101â109 (2003).
8. P. Mildenberger, M. Eichelberg, E. Martin. Introduction to the DICOM standard," Eur Radiol., 12 (4) 920â927 (2002). Epub 2001 Sept. 15.
9. B.L.T. Guthrie, C. Price, J. Zaleski, E. Backensto, "Digital Imaging and Communications in Medicine (DICOM) Archive is a Dynamic Component of a Clinician Image-related Workflow Solution," J Digit Imaging, 14 (2 Suppl 1)190â193 (2001).
10. J. Eng, J.P. Leal, W. Shu, G. Yang Liang, "Collaboration System for Radiology Workstations," Radiographics, 22 (5) e5 (2002).
Thomas T. Zacharia,* MD, is with the Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 (correspondence should be sent to: 5A Park Terrace, Arlington, MA 02474, email: firstname.lastname@example.org). James E. Sumner, BE, is with WorldCare Clinical, Cambridge, MA 02142. Sanjay Saini, MD, is with the Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
*To whom correspondence should be addressed.