Extraosseous uptake of technetium-99m methylene diphosphonate by an acute territorial cerebral infarct in a classical biodistribution pattern.

Technetium-99m methylene diphosphonate scintigraphy is usually performed to assess bone lesions, especially skeletal metastases in patients with a history of malignancy. However, it is important to recognize some specific conditions with a unique pattern of tracer uptake, especially in extraosseous locations as they are not related to primary neoplasm or metastases. Diagnosing such unusual presentation is essential as it significantly influences the clinical management. This case report describes an unusual presentation detected in a bone scan of an elderly female patient, who was a treated case of breast cancer and was referred for a bone scan to rule out bone metastases. Incidentally, a large acute territorial cerebral infarct was diagnosed, which was later confirmed by magnetic resonance imaging on diffusion-weighted images. Diagnosis of the typical presentation and timely management saved the patient life.

INTRODUCTION

An abnormal extraosseous tracer uptake may be encountered in many organs during the technetium-99m methylene diphosphonate (Tc-99m MDP) bone scan. Though such extraosseous uptake in the brain is rare, it may occur due to malignancy, calcification or infarct. Few instances of diagnosis of acute infarcts in the brain in Tc-99m bone scan have been documented in the literature. However, the presented case is unique in that the diagnosis of acute brain infarct was not clinically suspected initially during the referral considering the chronic debilitated status of the patient and the area of involvement in the brain was also significantly large.

CASE REPORT

A 77-year-old woman was referred for Tc-99m MDP whole body nuclear bone scan to rule out metastases. She underwent bilateral mastectomy 3 years ago for bilateral breast carcinoma and received chemotherapy also. She had multiple comorbidities including diabetes mellitus, hypertension and hypercholesterolemia and was bed-ridden, due to her chronic debilitated status.

In the anterior and posterior images of the whole body bone scan, a normal physiological pattern of tracer uptake was observed in the bones and degenerative changes were observed in bilateral shoulders, left knee and left ankle. No focus of intense uptake of tracer in bones suspicious of metastases was identified in axial and appendicular skeleton [Figure 1]. However, a heterogeneous and diffuse tracer uptake was noted in the right hemicranium and following which spot films of skull lateral views were obtained. The distribution of tracer uptake in the right lateral view of skull corresponded with the anterior circulation territory of the brain, sparing the posterior circulation territory of posterior fossa with a sharp demarcation [Figure 2]. Since the finding raised a strong suspicion of right anterior circulation territorial infarct of brain, patient was subjected to clinical examination, which revealed that the power of the left lower and upper limbs were reduced when compared to the right side.

Figure 1

Whole body bone scan shows an abnormal, diffuse and a heterogeneous tracer uptake in the right half of the skull, having straight margins in the midline (left arrow) and in the skull base (up arrow) suggesting tracer localization in a large area of the brain

Figure 2

Lateral spot views of skull shows tracer localization in the right anterior circulation territory of the brain with a clearly defined inferior margin (up sloping arrows) representing the border between anterior and posterior circulation

Patient was referred to the intensive care unit immediately for acute medical care. Later, patient was further investigated with magnetic resonance imaging (MRI), which confirmed the presence of an acute cerebral infarct confined to the right internal carotid arterial territory [Figure 3a–d]. Patient was discharged after conservative management.

Figure 3

Magnetic resonance imaging of brain (a) fluid attenuated inversion recovery, (b) T2 weighted, (c) diffusion-weighted image, (d) apparent diffusion coefficient sequences show a large area of right anterior cerebral circulation territory having restricted diffusion, confirming an acute infarct

DISCUSSION

Tc-99m MDP bone scan is the most commonly done nuclear scan in many nuclear medicine departments across the world. In this type of scan, usually 50-60% of tracer is localized in the bones and the remainder is cleared by the kidneys in 2-3 h. The benign and pathological lesions of the bones are diagnosed by increased uptake of the tracer by the lesions due to various reasons such as increased blood flow, increased osteoid formation or increased mineralization.[1]

Occasionally, an extraosseous abnormal tracer uptake in many organs can be encountered. This may be due to neoplastic, inflammatory, infective, traumatic, hormonal or ischemic lesions and artifacts. Enhanced regional vascularity and permeability, extracellular fluid expansion, elevated tissue calcium concentration, presence of tracer avid other metallic ions, adsorption onto immature collagen and binding to denatured proteins are some of the mechanisms, which lead to extraosseous uptake.[23] Such extraosseous uptake in the brain is rare, occurring in less than 0.2% of patients undergoing bone scintigraphy.[4] Acute infarcts of the brain show increased tracer uptake because of the following pathophysiology: (i) the ischemic damage to cellular membranes result in rapid intracellular influx of calcium leading to calcium precipitation within the mitochondria and (ii) denatured proteins also act as substrates for calcium deposition.[3] Established territorial infarcts of the brain show uptake of tracer in a well-defined pattern in the skull region depending upon the blocked artery.[45] If the ischemic changes are widespread and bilateral, for example in hypoxic ischemic encephalopathy, Tc-99m MDP is seen in laminar distribution and watershed territories matching the vascular insult.[6]

Increased tracer uptake in the brain is not specific to infarct alone. It can also be seen in other conditions, which produce damage to the blood brain barrier such as primary neoplasm, metastases or inflammation.[7] Sometimes tracer is localized in extra axial locations also such as hematomas, meningiomas, metastases and dural calcifications.[38] One rare instance of primary cerebral amyloidoma having increased bone tracer accumulation has been documented in the literature.[9]

Tc-99m MDP bone scan is often requested to rule out skeletal metastases in elderly patients having known or suspected cancer. The real challenge lies in diagnosing clinically unsuspected lesions amidst the primary concern of detecting metastases. Even a solitary focus of tracer uptake in the brain region can be due to causes other than metastases. As shown in this case report, brain infarction remains important differential diagnoses of the brain or skull metastases because silent brain infarction comprises 22% of all strokes. Careful clinical evaluation, additional single photon emission computed tomography imaging and further evaluation with computed tomography or MRI would be helpful for confirmation of diagnoses.[10]

CONCLUSION

In conclusion, it is important for the attending physician and the nuclear physician to be aware of the abnormal extraosseous uptake of Tc-99m MDP during bone scan, in order to make a sound diagnosis.