Nuclear medicine is the application of radiotracer methods to imaging the normal and pathologic distribution of radiopharmaceuticals in the body. Labeled pharmaceuticals are specific in their biodistribution and activity,providing information about physiologic and pathophysiologic processes (Table 8.1). In neuro-ophthalmology, these techniques offer functional information that is complementary to other imaging modalities, as disturbances in normal physiologic processes may be appreciated in the absence of detectable structural alterations. Nuclear scintigraphy is distinguished from plane film radiography and computed tomography in that the latter utilize x-rays generated from an external source, transmitted through the patient, while nuclear studies are emission scans obtained by the detection of gamma photons released from the nucleus of atoms during a nuclear transformation.
Table 8.1. AVAILABLE RADIOPHARMACEUTICALS FOR NUCLEAR MEDICINE STUDIES IN NEURO-OPHTHALMOLOGY
Principles and Technique
Summarizing key principles, radiopharmaceuticals are intravenously injected at very low mass doses, generally several thousand-fold below the minimal threshold for pharmacologic effects. Radiotracers undergo radioactive decay with the production of a gamma photon at a characteristic energy, which is emitted from the patient and detected by a gamma camera. The most commonly used isotope in nuclear studies is technetium-99m (99mTc) in the oxidized form as pertechnetate. This isotope is a pure gamma emitter with a favorable radiation safety profile. Gamma photons are highly penetrating, with less local tissue deposition of energy than with alpha or beta particulate emissions. The 140-keV photon released by 99mTc is ideal for imaging, with an energy high enough for emission through biologic tissue but not so high as to produce loss of spatial resolution by penetrating through the sides of the gamma camera and collimator. The gamma detector consists Of four major components: (a) a lead collimator through which photons may pass only at angles 90% incident to the collimator face, (b) a scintillation crystal that produces light when struck by photons, (c) photomultiplier tubes that convert and amplify the light signal into an electron pulse, and (d) position logic circuits with analog-to-digital converters that produce a planar image for display. Spatial resolution results from collimation of photons that penetrate to strike the scintillation crystal only at specified angles (90% for parallel-hole collimators) (Fig. 8.16). The large majority of photons are either scattered in the body or unable to penetrate the collimator, requiring 5 to 10 minutes to generate an acceptable delayed-phase image, although dynamic studies of blood flow may be accomplished with acquisition times as short as 3 to 5 seconds.
Figure 8.16. Diagram of gamma camera with major components; emitted photons strike the crystal face after passing through the collimator. Only photons 90% incident to the collimator will pass through. Alter striking the crystal, energy is converted into a light emission that is converted by the photomultiplier tubes Into an electron pulse for subsequent processing and image display.
Photons must travel through the body, which is an attenuating media of approximately water density, leading to degradation of the spatial resolution of the image. Planar data may be further enhanced by obtaining a series of multiple, short planar scans circumferentially around the patient and applying a mathematical reconstruction of the data obtained from these views to create a three-dimensional volume of data. This volume may be resliced at any angle. The method, referred to as single-photon-emission computed tomography (SPECT), improves the resolving ability of the instrument for detecting small foci of activity in activity within deep structures. SPECT imaging is particularly suited to neuro-ophthalmology applications, where structures adjacent to the orbits and fossa at the base of the skull may be poorly visualized with standard planar scintigraphy.
Another tomographic method in nuclear medicine is positron-emission tomography (PET), which is also capable of rendering three-dimensional data volumes. PET differs from SPECT in the use of positron-emitting radiopharmaceuticals, which are released from the nuclei of atoms into the adjacent soft tissue and undergo combination with an electron (annihilation event) with the release of two high-energy photons (511 keV) exactly 180° apart from each other. In PET, the crystal detectors are arranged around the patient and connected via a series of coincident circuits linking . crystals directly opposed to one another. This arrangement can distinguish the position of the emitted photons on the basis of the temporal characteristics of crystal stimulation. Hence, PET renders positional information in a very different fashion from SPECT. In general PET is more sensitive than SPECT and has better spatial resolution. The requirement of an on-site cyclotron for generation of the very short half-life PET isotopes limits the wide-spread availability of this method.
Indications and Applications
Nuclear medicine methods have been utilized in a variety of indications in neuro-ophthalmology, including evaluation of the bony orbital cavity for infection or bone graft integrity following reconstruction procedures, assessment of benign and malignant orbital masses, and in specialized applications using newer receptor-specific agents including the somatostatin-receptor-agent analogs.
Evaluation of focal infection, including osteomyelitis of the banes composing the orbital cavity is possible by radionuclide methods. Three-phase bone scan imaging is performed during the angiographic, vascular blood pool, and delayed phase (after 2 Righthours) after administration of a 99mTc-labeled diphosphonate compound. Diphosphonates are incorporated by chemisorption into bone matrix dependent on the local blood flow; the intensity of osteoblastic activity is an important determinant of metabolic activity and regional blood flow. Osteomyelitis presents as increased uptake on all phases of the bone scan, with increasingly focal accumulation on delayed images. Three-phase bone scintigraphy is highly sensitive, although nonspecific for the detection of osteomyelitis. Coupled with a radiolabeled leukocyte scan (Fig. 8.17) (commonly performed with 99mTc-HMPAO leukocytes, less commonly with indium-111-labeled leukocytes), the specificity of the technique for detection of osteomyelitis is 80 to 85%.
Figure 8.17. Osteomyelitis demonstrated by 99mTc-HMPAO-labeled leukocytes SPECT imaging in the left sphenoid bone of a diabetic patient presenting with headache and fever.
Orbital reconstruction using a substrate matrix with transplanted bony tissue can provide a physiologically viable and stable orbital cavity in patients with bone destruction. The reconstruction may be nonviable, secondary to impaired revascularization of the graft. Scintigraphic evaluation using 99mTc-diphosphonate compounds is useful for assessing the vascular integrity and viability of the bone graft. For these studies, an immediate angiographic phase nuclear study is performed, followed by delayed views after full incorporation of tracer into bone. Regions of impaired viability are indicated by poor initial perfusion to the region and reduced uptake on the delayed images, compared with surrounding bone. SPECT imaging may be particularly helpful in evaluating deep bone structures.
Oncologic diagnosis in neuro-ophthalmology may be enhanced with nuclear Methods. In patients with prior surgical procedures, anatomic imaging modalities may poorly distinguish between surgical changes and tumor recurrence. PET imaging with the !libeled glucose analog 18F-FDG has been successfully utilized in this fashion, demonstrating intense accumulation of FDG indicating high metabolic rates of metastatic or recurrent tumors. Nuclear scintigraphy using gamma emitters may also be helpful for characterizing the nature of a lesion. The benzamide dopamine DID, receptor agent I 23-/-N-(diethylamino-2-ethyl)4 iodobenzamide, was evaluated by Rodot and colleagues for the detection of metastatic malignant melanoma. In a group of 48 patients divided into subgroups with and without known metastases, the sensitivity for detecting lesions of the eye and orbit was greater Than 80%. Deol et al. reported the use of 99mTc-labeled autologous red cells to diagnose a benign vascular hamartoma in a patient presenting with unilateral proptosis lincl a lesion of the apex of the orbit. Increasing tracer accumulation in the vascular lesion over time is highly specific for hemangioma.
Newer radiotracers may be useful for evaluation of activated lymphocyte infiltration in endocrine ophthalmopathy. Using 111I-octreotide to evaluate somatostatin receptors expressed by ,lymphocytes in 40 patients with endocrine ophthalmopathy, Diaz and colleagues showed markedly increased orbital accumulation of the tracer in the orbits in patients with clinically active ophthalmopathy in Graves' disease or orbital myositis. Patients without clinically active disease evidence modest radiotracer uptake. The significance of this may lie in describing an objective marker for identification of patients who would benefit from treatment and the subsequent serial evaluation of therapeutic response.
This radiopharmaceutical has also been used for assessment of patients with visual disturbances related to chiasmal compression of pituitary tumors. The identification of somatostatin receptors in pituitary and parasellar tumors predicts a good suppressive effect of therapeutic levels of octreotide on hormone release by these tumors. Data also suggest as many as 75% of nonfunction-ing pituitary adenomas are visualized with 111I-DTPA-octreotide, although the treatment implications in this category are unclear.
Periphlebitis retinae (PR) is a condition Seen in multiple sclerosis (MS) patients, characterized by transitory infiltrates around the retinal veins. Infiltration of veins within the central nervous system also occurs and may be the process that presages white matter plaque formation. Engell and colleagues demonstrated a correlation between abnormalities in brain SPECT perfusion imaging in MS patients with active PR but not inactive disease. They suggest that disruption of the blood-brain barrier may account for these differences.
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