hr. J Radiation Onrolog~ Bid Phw. Vol. 22. pp. 251-257 Prmted m the U S A All rights reserved.
Copynght
036%3016/92 $5.00 + .OO 0 1991 Pergamon Press plc
??Original Contribution
NEW IMAGING TECHNOLOGIES: PROSPECTS FOR TARGET DEFINITION R. MARK HENKELMAN, PH.D. Department of Medical Biophysics and Sunnybrook Health Science Center, University of Toronto, 2075 Bayview Ave, Toronto, Ontario M4N 3M5 Canada Developments in medical imaging over the past 2 decades are providing significant improvement in tumor definition. Improvements in soft tissue visualization with tumor specific contrast combined with direct 3D data acquisition and millimetre spatial resolution set new standards in tumor definition. Such precision in tumor imaging provides a new level of challenge for precision radiation treatment. Significant further improvement over the next decade in geographic definition is unlikely. The challenge for imaging research is that of extracting tissue specific information about tumors such as perfusion and response to therapy rather than simply anatomical clarity. Oncological imaging, Magnetic resonance, Precision radiotherapy.
INTRODUCTION
This paper illustrates, using primarily MR as an example, how far imaging has come in tumor definition. The clinical examples that have been included have been selected to show the capabilities of tumor imaging and in no way is it suggested that these are appropriate candidates for proton radiation treatment. The achievements in imaging merely set a challenge for what should be attempted in the development of precision radiation treatment design.
There is probably no area of medicine that has experienced greater technological change over the past 2 decades than medical imaging. The development of x-ray computed tomography (CT) has been appropriately recognized by the awarding of the Nobel Prize in Medicine, and the impact of CT on precision radiation therapy is now well appreciated by all radiation oncologists. But even before CT was fully assimilated into medical practice, along came magnetic resonance (MR) imaging with a whole new range of capabilities and unique challenges (1). The assistance provided by MR to the definition of precise radiation treatment is still being actively explored. Less dramatically, but no less importantly, ultrasound (US) imaging has continued to develop over the same period of time to a stage where it also plays an essential and increasing role in tumor definition. Technological developments in imaging provide the basis for precision radiation treatment. There is little point in talking about precise dose distributions if the target volume cannot be defined with equivalent or better precision. It is appropriate, therefore, to pause and ask, “How far has imaging progressed in its ability to define tumors? What can we expect of imaging over the next decade?”
DISCUSSION MR for tumor imaging Because MR is the newest imaging method with the greatest technological change, and because it is the primary area of the author’s expertise, the present state of the art in tumor definition is presented from the perspective of MR. Magnetic resonance has several advantages for tumor imaging and a couple of disadvantages that are summarized in Table 1. The disadvantages are well appreciated (6). Lack of electron density information in MR make CT a preferable data base for radiation transport calculations and inhomogeneity corrections. Distortion in MR images arising from perturbation of the homogeneous magnetic field either from ferromagnetic materials within the patient
Presented at the NIH/NCI Proton Workshop, Bethesda, Maryland 27-29 April, 1989. Acknowledgements-A number of individuals are thanked for providing high quality and demonstrative images for this work:
Montreal Neurological Institute; Dr. Tom Masayk, Case Western Reserve; and Dr. Benedick Fraass, Ann Arbor. Supported by the National Cancer Institute of Canada, the Medical Research Council of Canada and General Electric Medical Systems of Canada. Accepted for publication 22 May 1990.
Dr. Walter Kucharczyk, Dr. George Wortzman, Dr. Stephanie Wilson, Dr. Charles Pavlin, Dr. Peter Poon, all of the Radiology Department of the University of Toronto, and Dr. Terry Peters,
251
I. J. Radiation Oncology 0 Biology 0 Physics
252
Volume 22, Number 2, 1992
Table 1. Advantages and disadvantages of MR imaging for precision radiation therapy Disadvantages
Advantages Good soft tissue visualization Tumor specific contrast 3D representation Excellent resolution
or metallic
objects
monitored
using a fiducial
No density information Potential spatial distortion
in the environment reference
of the imager
can be
system. Awareness of sufficient for avoiding
this potential liability is probably planning errors. The advantages of magnetic resonance for tumor imaging are listed in Table 1 and will be discussed in turn with clinical examples. (I) Good soft tissue visualization. X-ray based imaging techniques have maximum sensitivity to bone and injected contrast agents due to their high atomic number. Tumors that are soft tissue growths show negligible difference in atomic number from their host soft tissues (2). MR, on the other hand, is maximally sensitive to soft tissues and fluids and insensitive to bone, making it ideally suited for tumour imaging. Figure 1 shows a hemangioblastoma in the posterior fossa. The central solid tumor nodule is clearly distinguished from the surrounding large proteinaceous cyst. The large vessels appearing as black dots are characteristic of such tumors. Even though this tumor is located in the posterior fossa (which is known to be a region difficult to image with CT because of beam hardening from surrounding bone) the sensitivity of MR to soft tissues and the lack of
Fig. 1. A hemangioblastoma in the posterior fossa is clearly distinguished consisting of large proteinaceous fluid filled cyst and a solid nodular tumor. Interference from the hard bone at the base of the skull, which would make this tumor difficult to image with CT, is not a problem in magnetic resonance because of its insensitivity to bone.
Fig. 2. A coronal image of a normal prostate taken with surface coils, fat suppression, reduced band width, and a T,-weighted spin echo sequence shows the bright outer periprostatic venous plexus, the outer and inner zones of the prostate gland and the urethra with remarkable detail. Again, the absence of interference from pelvic bones is a distinct advantage in MR’s ability to visualize soft tissue structure.
bony influence on MR allow excellent delineation of this tumor. Similarly, Figure 2 shows a coronal MR image of a normal prostate gland. Again, CT of the prostate is generally disappointing due to interference from the hip bones. The soft tissue sensitivity of MR allows direct visualization of the periprostatic venous plexus as a bright rim above the prostate (11); the outer zone of the gland is slightly brighter than the inner zone and the urethra passing through the center of the gland. In spite of the excellent anatomical definition of the gland, prostatic cancer and benign prostatic hypertrophy cannot be reliably differentiated from normal gland because the MR tissue parameters are not sufficiently different in this anatomical site (9). Many other examples could be provided of soft tissue visualization with MR without any interference from surrounding bone-a hallmark of MR imaging. In this respect, MR is ideally suited for imaging localized disease within the bone marrow (5, 10). Tumor specific contrast Because magnetic resonance images naturally occurring protons in the body, primarily in water molecules, its major sensitivity is to soft tissues and fluids. Very early work on nuclear magnetic resonance and cancer showed that tumors have characteristically longer MR relaxation times than do corresponding normal tissues (3, 7). Although the reasons for this fact are not understood, these tissue differences provide the basis for tumor contrast in MR. Figure 3 shows three comparative axial brain images of a patient with cerebral metastases from a primary breast tumor. The CT image on the left does not provide sufficient soft tissue contrast to visualize the metastatic lesions.
New imaging technologies 0 R. M.
HENKELMAN
253
Fig. 3. Brain metastases from a primary breast tumor are not evident on a CT scan (left). Magnetic resonance shows up metastases with high tumor specific contrast on both a T,-weighted sequence (center), and to a lesser degree on a T,-weighted sequence (right).
MR can exploit the increased T, relaxation time of the metastatic tissue to show the lesions with bright contrast on a T,-weighted sequence (TE = 80, TR = 2000) in the center. Alternatively on the right, the increased T, relaxation of the lesions can be exploited to produce a dark lesion contrast in a T,-weighted imaged (TE = 20, TR = 500). As evidenced in this example, T,-weighted MR imaging usually provides better tumor contrast and hence visualization than is achieved in T,-weighted imaging. Unfortunately, T,-weighted images take longer to obtain and provide poorer anatomical resolution. Relaxation time differences are not the only source of MR image contrast. MR is very sensitive to motion and flow, limiting its range of usefulness in the body. However, flow sensitivity can be used to advantage. Figure 4a shows a conventional digital subtraction neuroangiogram depicting a large arterio venous malformation (AVM). Figure 4b shows an MR angiogram of the same patient produced without contrast agent but making use of flow sensitive contrast (12). The AVM is readily identifiable even on an image at the present state of early development. Screening for AVM’s which will be treated with precision radio surgery may become a routine adjunct to MR studies of the brain. Tumor specific contrast in MR is not without ambiguities. Figure 5a shows a small and apparently localized glioblastoma in the left posterior white matter. A T,-weighted image of the same slice (Figure 5b) shows a much more extended region of high signal intensity. This extended region is generally understood to be peripheral edema (8). What has not been determined is whether it is appropriate to include the extended region in the target volume because it is indicative of spread of disease, or exclude it because it is non-specific peripheral edema. In either case, the increased tumor contrast available with MR raises questions about the definition of tumor target volume.
Three-dimensional representation The design of precision radiation treatments is an intrinsically 3-dimensional problem. Detailed planning in a trans-
(4
(b) Fig. 4. An arteriovenous malformation is clearly identified by digital subtraction neuroangiography (a). It is also well identified in a flow sensitive MR angiogram (b), obtained without the use of any contrast agent. (Image provided by Dr. Masayk, Cleveland.)
I. J. Radiation Oncology 0 Biology 0 Physics
(4
Volume 22, Number 2, 1992
(a)
(b) Fig. 5. A T,-weighted sequence (a) shows a glioblastoma which is relatively well localized. In contrast, the T,-weighted sequence (b) shows a much greater extended region of tissue involvement surrounding the tumor. Whether such regions of peripheral edema should be included in the tumor target volume still has to be determined.
axial section is unwarranted if one is going to assume that the anatomy is cylindrical in the crania-caudid direction. Developments in imaging are rapidly addressing the 3-dimensional nature of patient anatomy. MR has the ability of imaging in any arbitrarily oriented direction. Figures 6a and 6b show axial and sagittal images through a brainstem glioma. Exact definition of tumor extent in the axial direction is matched by equivalent definition in the orthogonal direction. This type of 3-dimensional visualization is a prerequisite for the planning of intrinsically 3-dimensional precision radiotherapy. Integrated 3-dimensional visualization of anatomy demands more than just orthogonal images. MR is capable of acquiring truly 3-dimensional volume images with equivalent resolution in all directions, but methods of 3-dimensional computer graphics display are not yet completely established. One approach, based on segmentation of the image into anatomical units, identification of the 2-dimen-
Fig. 6. Axial (a), and sagittal (b) MR images of a brainstem glioma give good visualization of the 3-dimensional extent of the tumor in all three dimensions.
Fig. 7. A full 3-dimensional MR acquisition is displayed with surface rendering. The development of sophisticated tissue segmentation algorithms to determine which tissue should be grouped together is a necessary prerequisite for such surface rendering.
New imaging technologies 0 R. M.
HENKELMAN
Fig. 8. A benign globus tympanicum is readily identified (arrow) on high resolution CT even though its dimensions are only 3 mm X 5mm.
(a)
(b) Fig. 9. (a) High resolution ocular ultrasound provides good definition of the extent of an interorbital retinoblastoma. Detachment of the retina due to the tumor is readily appreciated. (b) A transrectal ultrasound is readily able to answer questions about the extension of a rectal carcinoma beyond the rectal wall even though the components of the wall have a thickness of less than 1 mm. This image shows an intact wall designating this rectal carcinoma to be a stage two.
(b) Fig. 10. Coronal MR images show a pituitary adenoma of ‘6 mm dian leter. (a) the T,-weighted sequence does not show the tu mor with specific contrast but reveals an enlarged pituitary ant ia deviate :d pituitary stock. (b) the T,-weighted sequence give sl 3oor omit definition but shows the nodule with its intrinsic tu mor cant rast
256
I. J. Radiation Oncology 0 Biology 0 Physics
sional surface and rendering the surface in a dynamic radio display is shown in Figure 7. Whether this approach is appropriate for the presentation of 3-dimensional tumor and target volumes or some other type of graphics presentation is still to be determined. In either case rapid developments in computer hardware are making various approaches to high resolution display of three dimensional data a realistic possibility. Graphic workstations will be the working context for the planning of precision radiation therapy (4). Excellent resolution Probably the most significant measure of progress in imaging technology is the gain in spatial resolution that has been achieved in all of the sectional imaging technologies. Figure 8 shows a high resolution CT section through the inner ear which clearly delineates a benign globus tympanicum which is only 3 x 5 mm’. Details of adjacent bony septa demonstrate better than 0.5 mm resolution. This level of spatial resolution has only been routinely achieved with CT in the past 5 years. CT is not the only modality to have achieved significant improvement in spatial resolution. Ultrasound also shows dramatic spatial resolution particularly in applications where localized special purpose transducers are being used. Figure 9a shows an intraorbital retinoblastoma with remarkable definition. The detailed retinal detachment adjacent to the tumor is also readily appreciated even though it is a sub-millimeter structure. As another example, Figure 9b presents a transrectal ultrasound image of a rectal carcinoma. The tumor mass is well visualized within the rectum but more importantly, the layers of the rectal wall are clearly distinguished showing that the wall has not been invaded by the tumor. High resolution imaging of normal organ boundaries provides the necessary information for accurate tumor staging. Magnetic resonance also achieves excellent spatial resolution. Figures 10a and b show coronal images in a patient with a pituitary adenoma of 6 mm diameter. The T,weighted (600/20) image does not reveal the tumor with any contrast but does show an asymmetric gland arching over the right internal carotid artery and a deviated stalk.
Volume 22, Number 2, 1992
The T,-weighted (2000/80) sequence has overall poorer signal to noise leading to inferior achievable resolution but shows the tumor with dark contrast with respect to the gland. Taken together, the MR images show an effective resolution of l-2 mm. Thus, each of the sectional imaging modalities has developed to a stage where tumor spatial definition at the order of a millimeter can be expected and regularly achieved.
CONCLUSION As demonstrated by the examples presented above, medical imaging technology has made impressive strides over the past decade. It is now reasonable to expect tumor definition with good contrast, resolution of l-2 mm, and full 3-dimensional representations. A few exceptions persist such as pancreatic tumors and retroperitoneal lymph nodes where methods of tumor specific contrast have yet to be developed. Developments in imaging set a new challenge for the ability of radiation oncology to provide precision radiation treatment. In the future, medical imaging will continue to improve but at a slower rate. Most of the present-day research is designed to improve resolution or contrast by at most factors of two. In fact, most imaging researchers would consider their research to be remarkably successful if tumor definition could be routinely established at below 1 mm resolution. Such a gain however, makes only an insignificant impact on the needs in cancer imaging. The identification of micrometastases for reliable tumor staging would require orders of magnitude improvement in spatial resolution which is not likely even on the distant horizon. Imaging now provides the requisite anatomical information needed for refined precision radiation treatment. The challenges for imaging are to move beyond questions of mere geometric definition to answer questions about tumor physiology and function, potential response to therapies, and actual follow-up after treatment. Such tumor characterization, if it can be accomplished, will allow imaging to contribute to many more aspects of cancer management than just target definition.
REFERENCES Abrams, H. L.; er al. Magnetic resonance imaging. National Institutes of Health Consensus Development Conference Statement 6(14):1-55; 1987. Bronskill, M. J.; Brown, D. W.; Yaffe, M. J.; Johns, P. C.; Foster, F. S.; D’Astous, F. T. Comparison of NMR with ultrasound and x-ray. In: Allen, P. S., Boisvert, D. P. J., Lende, B. C., eds. Proceedings of the International Conference on Magnetic Resonance in Cancer. Banff, Canada: Pergamon Press; 1986:47. Damadian, R. Tumour detection by magnetic resonance. Science 171:1151-l 153; 1971. Fraass, B. A.; McShan, D. L.; Weeks, K. J. 3-D treatment planning:III. Complete beam’s-eye-view planning capabilities. In: Bruinvis, I. A. D., van der Giessen, P. H., van Kleffens, H. J.. Wittkamper, F. W., eds. The use of com-
puters in radiation therapy. North-Holland: Elsevier Science Publ. B. V.; 1987:193-196. 5. Henkelman, R. M.; Messner, H.; Poon, P. Y.; Hit&s, R. S.; Stewart, C.; Curtis, J.; Minden, M.; Baker, M. Magnetic resonance imaging for monitoring relapse of acute myeloid leukemia. Leukemia Res. 12(10):811-816; 1988. 6. Henkelman, R. M.; Poon, P. Y.; Bronskill, M. J. Is magnetic resonance imaging useful for radiation therapy planning? In: Proceedings of Eighth International Conference on the Use of Computers in Radiation Therapy. IEEE Computer Society; 1984:181-185. 7. Hollis, D. P.; Economou, J. S.; Parks, L. D.; Eggleston, J. C.; Saryan, L. A.; Czeisler, J. L. Nuclear magnetic resonance studies of several experimental and human malignant tumors. Cancer Res. 33:2156-2160; 1973.
New imaging technologies 0
8. Johnson, P. C.; Hunt, S. J.; Drayer, B. P. Human cerebral gliomas: correlation of post-mortem MR imaging and nemopathologic findings. Radiology 170:211-217; 1989. 9. Ling, D.; Lee, J. K. T.; Heiken, J. P.; Balfe, D. M.; Glazer, H. S.; McClennan, B. L. Prostatic carcinoma and benign prostatic hyperplasia: inability of MR imaging to distinguish between the two diseases. Radiology 158:103-107; 1986. 10. Mitchell, M. D.; Kundel, H. L.; Steinberg, M. E.; Kressel,
H. Y.; Alavi, A.; Axel, L. Avascular necrosis of the hip:
R. M. HENKELMAN
257
comparison of MR, CT and scintigraphy. Am. J. Roentgenol. 147:1967. 11. Poon, P. Y.; Bronskill, M. J.; Poon, C. S.; McCallum, R. W.; Henkelman, R. M. Identification of the periprostatic venous plexus by MRI. J. Comp. Assist. Tomo. 1526% 268; 1991. l2 Ruggieri, P. M.; Laub, G. A.; Masayk, T. J.; Medic, M. T. Intracranial circulation: pulse-sequence considerations in three dimensional (volume) MR angiography. Radiology 171:793-800; 1989.
Copynght
036%3016/92 $5.00 + .OO 0 1991 Pergamon Press plc
??Original Contribution
NEW IMAGING TECHNOLOGIES: PROSPECTS FOR TARGET DEFINITION R. MARK HENKELMAN, PH.D. Department of Medical Biophysics and Sunnybrook Health Science Center, University of Toronto, 2075 Bayview Ave, Toronto, Ontario M4N 3M5 Canada Developments in medical imaging over the past 2 decades are providing significant improvement in tumor definition. Improvements in soft tissue visualization with tumor specific contrast combined with direct 3D data acquisition and millimetre spatial resolution set new standards in tumor definition. Such precision in tumor imaging provides a new level of challenge for precision radiation treatment. Significant further improvement over the next decade in geographic definition is unlikely. The challenge for imaging research is that of extracting tissue specific information about tumors such as perfusion and response to therapy rather than simply anatomical clarity. Oncological imaging, Magnetic resonance, Precision radiotherapy.
INTRODUCTION
This paper illustrates, using primarily MR as an example, how far imaging has come in tumor definition. The clinical examples that have been included have been selected to show the capabilities of tumor imaging and in no way is it suggested that these are appropriate candidates for proton radiation treatment. The achievements in imaging merely set a challenge for what should be attempted in the development of precision radiation treatment design.
There is probably no area of medicine that has experienced greater technological change over the past 2 decades than medical imaging. The development of x-ray computed tomography (CT) has been appropriately recognized by the awarding of the Nobel Prize in Medicine, and the impact of CT on precision radiation therapy is now well appreciated by all radiation oncologists. But even before CT was fully assimilated into medical practice, along came magnetic resonance (MR) imaging with a whole new range of capabilities and unique challenges (1). The assistance provided by MR to the definition of precise radiation treatment is still being actively explored. Less dramatically, but no less importantly, ultrasound (US) imaging has continued to develop over the same period of time to a stage where it also plays an essential and increasing role in tumor definition. Technological developments in imaging provide the basis for precision radiation treatment. There is little point in talking about precise dose distributions if the target volume cannot be defined with equivalent or better precision. It is appropriate, therefore, to pause and ask, “How far has imaging progressed in its ability to define tumors? What can we expect of imaging over the next decade?”
DISCUSSION MR for tumor imaging Because MR is the newest imaging method with the greatest technological change, and because it is the primary area of the author’s expertise, the present state of the art in tumor definition is presented from the perspective of MR. Magnetic resonance has several advantages for tumor imaging and a couple of disadvantages that are summarized in Table 1. The disadvantages are well appreciated (6). Lack of electron density information in MR make CT a preferable data base for radiation transport calculations and inhomogeneity corrections. Distortion in MR images arising from perturbation of the homogeneous magnetic field either from ferromagnetic materials within the patient
Presented at the NIH/NCI Proton Workshop, Bethesda, Maryland 27-29 April, 1989. Acknowledgements-A number of individuals are thanked for providing high quality and demonstrative images for this work:
Montreal Neurological Institute; Dr. Tom Masayk, Case Western Reserve; and Dr. Benedick Fraass, Ann Arbor. Supported by the National Cancer Institute of Canada, the Medical Research Council of Canada and General Electric Medical Systems of Canada. Accepted for publication 22 May 1990.
Dr. Walter Kucharczyk, Dr. George Wortzman, Dr. Stephanie Wilson, Dr. Charles Pavlin, Dr. Peter Poon, all of the Radiology Department of the University of Toronto, and Dr. Terry Peters,
251
I. J. Radiation Oncology 0 Biology 0 Physics
252
Volume 22, Number 2, 1992
Table 1. Advantages and disadvantages of MR imaging for precision radiation therapy Disadvantages
Advantages Good soft tissue visualization Tumor specific contrast 3D representation Excellent resolution
or metallic
objects
monitored
using a fiducial
No density information Potential spatial distortion
in the environment reference
of the imager
can be
system. Awareness of sufficient for avoiding
this potential liability is probably planning errors. The advantages of magnetic resonance for tumor imaging are listed in Table 1 and will be discussed in turn with clinical examples. (I) Good soft tissue visualization. X-ray based imaging techniques have maximum sensitivity to bone and injected contrast agents due to their high atomic number. Tumors that are soft tissue growths show negligible difference in atomic number from their host soft tissues (2). MR, on the other hand, is maximally sensitive to soft tissues and fluids and insensitive to bone, making it ideally suited for tumour imaging. Figure 1 shows a hemangioblastoma in the posterior fossa. The central solid tumor nodule is clearly distinguished from the surrounding large proteinaceous cyst. The large vessels appearing as black dots are characteristic of such tumors. Even though this tumor is located in the posterior fossa (which is known to be a region difficult to image with CT because of beam hardening from surrounding bone) the sensitivity of MR to soft tissues and the lack of
Fig. 1. A hemangioblastoma in the posterior fossa is clearly distinguished consisting of large proteinaceous fluid filled cyst and a solid nodular tumor. Interference from the hard bone at the base of the skull, which would make this tumor difficult to image with CT, is not a problem in magnetic resonance because of its insensitivity to bone.
Fig. 2. A coronal image of a normal prostate taken with surface coils, fat suppression, reduced band width, and a T,-weighted spin echo sequence shows the bright outer periprostatic venous plexus, the outer and inner zones of the prostate gland and the urethra with remarkable detail. Again, the absence of interference from pelvic bones is a distinct advantage in MR’s ability to visualize soft tissue structure.
bony influence on MR allow excellent delineation of this tumor. Similarly, Figure 2 shows a coronal MR image of a normal prostate gland. Again, CT of the prostate is generally disappointing due to interference from the hip bones. The soft tissue sensitivity of MR allows direct visualization of the periprostatic venous plexus as a bright rim above the prostate (11); the outer zone of the gland is slightly brighter than the inner zone and the urethra passing through the center of the gland. In spite of the excellent anatomical definition of the gland, prostatic cancer and benign prostatic hypertrophy cannot be reliably differentiated from normal gland because the MR tissue parameters are not sufficiently different in this anatomical site (9). Many other examples could be provided of soft tissue visualization with MR without any interference from surrounding bone-a hallmark of MR imaging. In this respect, MR is ideally suited for imaging localized disease within the bone marrow (5, 10). Tumor specific contrast Because magnetic resonance images naturally occurring protons in the body, primarily in water molecules, its major sensitivity is to soft tissues and fluids. Very early work on nuclear magnetic resonance and cancer showed that tumors have characteristically longer MR relaxation times than do corresponding normal tissues (3, 7). Although the reasons for this fact are not understood, these tissue differences provide the basis for tumor contrast in MR. Figure 3 shows three comparative axial brain images of a patient with cerebral metastases from a primary breast tumor. The CT image on the left does not provide sufficient soft tissue contrast to visualize the metastatic lesions.
New imaging technologies 0 R. M.
HENKELMAN
253
Fig. 3. Brain metastases from a primary breast tumor are not evident on a CT scan (left). Magnetic resonance shows up metastases with high tumor specific contrast on both a T,-weighted sequence (center), and to a lesser degree on a T,-weighted sequence (right).
MR can exploit the increased T, relaxation time of the metastatic tissue to show the lesions with bright contrast on a T,-weighted sequence (TE = 80, TR = 2000) in the center. Alternatively on the right, the increased T, relaxation of the lesions can be exploited to produce a dark lesion contrast in a T,-weighted imaged (TE = 20, TR = 500). As evidenced in this example, T,-weighted MR imaging usually provides better tumor contrast and hence visualization than is achieved in T,-weighted imaging. Unfortunately, T,-weighted images take longer to obtain and provide poorer anatomical resolution. Relaxation time differences are not the only source of MR image contrast. MR is very sensitive to motion and flow, limiting its range of usefulness in the body. However, flow sensitivity can be used to advantage. Figure 4a shows a conventional digital subtraction neuroangiogram depicting a large arterio venous malformation (AVM). Figure 4b shows an MR angiogram of the same patient produced without contrast agent but making use of flow sensitive contrast (12). The AVM is readily identifiable even on an image at the present state of early development. Screening for AVM’s which will be treated with precision radio surgery may become a routine adjunct to MR studies of the brain. Tumor specific contrast in MR is not without ambiguities. Figure 5a shows a small and apparently localized glioblastoma in the left posterior white matter. A T,-weighted image of the same slice (Figure 5b) shows a much more extended region of high signal intensity. This extended region is generally understood to be peripheral edema (8). What has not been determined is whether it is appropriate to include the extended region in the target volume because it is indicative of spread of disease, or exclude it because it is non-specific peripheral edema. In either case, the increased tumor contrast available with MR raises questions about the definition of tumor target volume.
Three-dimensional representation The design of precision radiation treatments is an intrinsically 3-dimensional problem. Detailed planning in a trans-
(4
(b) Fig. 4. An arteriovenous malformation is clearly identified by digital subtraction neuroangiography (a). It is also well identified in a flow sensitive MR angiogram (b), obtained without the use of any contrast agent. (Image provided by Dr. Masayk, Cleveland.)
I. J. Radiation Oncology 0 Biology 0 Physics
(4
Volume 22, Number 2, 1992
(a)
(b) Fig. 5. A T,-weighted sequence (a) shows a glioblastoma which is relatively well localized. In contrast, the T,-weighted sequence (b) shows a much greater extended region of tissue involvement surrounding the tumor. Whether such regions of peripheral edema should be included in the tumor target volume still has to be determined.
axial section is unwarranted if one is going to assume that the anatomy is cylindrical in the crania-caudid direction. Developments in imaging are rapidly addressing the 3-dimensional nature of patient anatomy. MR has the ability of imaging in any arbitrarily oriented direction. Figures 6a and 6b show axial and sagittal images through a brainstem glioma. Exact definition of tumor extent in the axial direction is matched by equivalent definition in the orthogonal direction. This type of 3-dimensional visualization is a prerequisite for the planning of intrinsically 3-dimensional precision radiotherapy. Integrated 3-dimensional visualization of anatomy demands more than just orthogonal images. MR is capable of acquiring truly 3-dimensional volume images with equivalent resolution in all directions, but methods of 3-dimensional computer graphics display are not yet completely established. One approach, based on segmentation of the image into anatomical units, identification of the 2-dimen-
Fig. 6. Axial (a), and sagittal (b) MR images of a brainstem glioma give good visualization of the 3-dimensional extent of the tumor in all three dimensions.
Fig. 7. A full 3-dimensional MR acquisition is displayed with surface rendering. The development of sophisticated tissue segmentation algorithms to determine which tissue should be grouped together is a necessary prerequisite for such surface rendering.
New imaging technologies 0 R. M.
HENKELMAN
Fig. 8. A benign globus tympanicum is readily identified (arrow) on high resolution CT even though its dimensions are only 3 mm X 5mm.
(a)
(b) Fig. 9. (a) High resolution ocular ultrasound provides good definition of the extent of an interorbital retinoblastoma. Detachment of the retina due to the tumor is readily appreciated. (b) A transrectal ultrasound is readily able to answer questions about the extension of a rectal carcinoma beyond the rectal wall even though the components of the wall have a thickness of less than 1 mm. This image shows an intact wall designating this rectal carcinoma to be a stage two.
(b) Fig. 10. Coronal MR images show a pituitary adenoma of ‘6 mm dian leter. (a) the T,-weighted sequence does not show the tu mor with specific contrast but reveals an enlarged pituitary ant ia deviate :d pituitary stock. (b) the T,-weighted sequence give sl 3oor omit definition but shows the nodule with its intrinsic tu mor cant rast
256
I. J. Radiation Oncology 0 Biology 0 Physics
sional surface and rendering the surface in a dynamic radio display is shown in Figure 7. Whether this approach is appropriate for the presentation of 3-dimensional tumor and target volumes or some other type of graphics presentation is still to be determined. In either case rapid developments in computer hardware are making various approaches to high resolution display of three dimensional data a realistic possibility. Graphic workstations will be the working context for the planning of precision radiation therapy (4). Excellent resolution Probably the most significant measure of progress in imaging technology is the gain in spatial resolution that has been achieved in all of the sectional imaging technologies. Figure 8 shows a high resolution CT section through the inner ear which clearly delineates a benign globus tympanicum which is only 3 x 5 mm’. Details of adjacent bony septa demonstrate better than 0.5 mm resolution. This level of spatial resolution has only been routinely achieved with CT in the past 5 years. CT is not the only modality to have achieved significant improvement in spatial resolution. Ultrasound also shows dramatic spatial resolution particularly in applications where localized special purpose transducers are being used. Figure 9a shows an intraorbital retinoblastoma with remarkable definition. The detailed retinal detachment adjacent to the tumor is also readily appreciated even though it is a sub-millimeter structure. As another example, Figure 9b presents a transrectal ultrasound image of a rectal carcinoma. The tumor mass is well visualized within the rectum but more importantly, the layers of the rectal wall are clearly distinguished showing that the wall has not been invaded by the tumor. High resolution imaging of normal organ boundaries provides the necessary information for accurate tumor staging. Magnetic resonance also achieves excellent spatial resolution. Figures 10a and b show coronal images in a patient with a pituitary adenoma of 6 mm diameter. The T,weighted (600/20) image does not reveal the tumor with any contrast but does show an asymmetric gland arching over the right internal carotid artery and a deviated stalk.
Volume 22, Number 2, 1992
The T,-weighted (2000/80) sequence has overall poorer signal to noise leading to inferior achievable resolution but shows the tumor with dark contrast with respect to the gland. Taken together, the MR images show an effective resolution of l-2 mm. Thus, each of the sectional imaging modalities has developed to a stage where tumor spatial definition at the order of a millimeter can be expected and regularly achieved.
CONCLUSION As demonstrated by the examples presented above, medical imaging technology has made impressive strides over the past decade. It is now reasonable to expect tumor definition with good contrast, resolution of l-2 mm, and full 3-dimensional representations. A few exceptions persist such as pancreatic tumors and retroperitoneal lymph nodes where methods of tumor specific contrast have yet to be developed. Developments in imaging set a new challenge for the ability of radiation oncology to provide precision radiation treatment. In the future, medical imaging will continue to improve but at a slower rate. Most of the present-day research is designed to improve resolution or contrast by at most factors of two. In fact, most imaging researchers would consider their research to be remarkably successful if tumor definition could be routinely established at below 1 mm resolution. Such a gain however, makes only an insignificant impact on the needs in cancer imaging. The identification of micrometastases for reliable tumor staging would require orders of magnitude improvement in spatial resolution which is not likely even on the distant horizon. Imaging now provides the requisite anatomical information needed for refined precision radiation treatment. The challenges for imaging are to move beyond questions of mere geometric definition to answer questions about tumor physiology and function, potential response to therapies, and actual follow-up after treatment. Such tumor characterization, if it can be accomplished, will allow imaging to contribute to many more aspects of cancer management than just target definition.
REFERENCES Abrams, H. L.; er al. Magnetic resonance imaging. National Institutes of Health Consensus Development Conference Statement 6(14):1-55; 1987. Bronskill, M. J.; Brown, D. W.; Yaffe, M. J.; Johns, P. C.; Foster, F. S.; D’Astous, F. T. Comparison of NMR with ultrasound and x-ray. In: Allen, P. S., Boisvert, D. P. J., Lende, B. C., eds. Proceedings of the International Conference on Magnetic Resonance in Cancer. Banff, Canada: Pergamon Press; 1986:47. Damadian, R. Tumour detection by magnetic resonance. Science 171:1151-l 153; 1971. Fraass, B. A.; McShan, D. L.; Weeks, K. J. 3-D treatment planning:III. Complete beam’s-eye-view planning capabilities. In: Bruinvis, I. A. D., van der Giessen, P. H., van Kleffens, H. J.. Wittkamper, F. W., eds. The use of com-
puters in radiation therapy. North-Holland: Elsevier Science Publ. B. V.; 1987:193-196. 5. Henkelman, R. M.; Messner, H.; Poon, P. Y.; Hit&s, R. S.; Stewart, C.; Curtis, J.; Minden, M.; Baker, M. Magnetic resonance imaging for monitoring relapse of acute myeloid leukemia. Leukemia Res. 12(10):811-816; 1988. 6. Henkelman, R. M.; Poon, P. Y.; Bronskill, M. J. Is magnetic resonance imaging useful for radiation therapy planning? In: Proceedings of Eighth International Conference on the Use of Computers in Radiation Therapy. IEEE Computer Society; 1984:181-185. 7. Hollis, D. P.; Economou, J. S.; Parks, L. D.; Eggleston, J. C.; Saryan, L. A.; Czeisler, J. L. Nuclear magnetic resonance studies of several experimental and human malignant tumors. Cancer Res. 33:2156-2160; 1973.
New imaging technologies 0
8. Johnson, P. C.; Hunt, S. J.; Drayer, B. P. Human cerebral gliomas: correlation of post-mortem MR imaging and nemopathologic findings. Radiology 170:211-217; 1989. 9. Ling, D.; Lee, J. K. T.; Heiken, J. P.; Balfe, D. M.; Glazer, H. S.; McClennan, B. L. Prostatic carcinoma and benign prostatic hyperplasia: inability of MR imaging to distinguish between the two diseases. Radiology 158:103-107; 1986. 10. Mitchell, M. D.; Kundel, H. L.; Steinberg, M. E.; Kressel,
H. Y.; Alavi, A.; Axel, L. Avascular necrosis of the hip:
R. M. HENKELMAN
257
comparison of MR, CT and scintigraphy. Am. J. Roentgenol. 147:1967. 11. Poon, P. Y.; Bronskill, M. J.; Poon, C. S.; McCallum, R. W.; Henkelman, R. M. Identification of the periprostatic venous plexus by MRI. J. Comp. Assist. Tomo. 1526% 268; 1991. l2 Ruggieri, P. M.; Laub, G. A.; Masayk, T. J.; Medic, M. T. Intracranial circulation: pulse-sequence considerations in three dimensional (volume) MR angiography. Radiology 171:793-800; 1989.
