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Our objective was to study the value of 99mtechnetium-pyrophosphate (99mTc-PYP) muscle scintigraphy and magnetic resonance imaging (MRI) in detecting areas of likely muscle inflammation and in increasing the rate of positive muscle biopsies in patients with suspected myositis. The results showed that in 13 out of 13 patients with clinical and/or signs of inflammatory muscle disease, increased 99mTc-PYP uptake was demonstrated at different muscle sites 3 h after isotope injection. Subsequent MRI of symmetric muscle areas with enhanced 99mTc-PYP uptake revealed signal patterns suggesting inflammation in all cases. Biopsy of these targeted muscles demonstrated characteristic histopathologic signs of muscle inflammation in 9 out of 13 patients. Four of these 9 patients had clinically atypical disease or did not show elevated creatine phosphokinase levels. Seven of these 9 patients had not been pretreated with corticosteroids. In 4 patients only muscle fiber atrophy and/or necrosis without cellular infiltrations was seen. These 4 patients had received either high doses of corticosteroids or low doses over longer periods of time before muscle biopsy. In conclusion, the combination of 99mTc-PYP muscle scintigraphy and MRI demonstrated muscle areas with maximum inflammatory signal patterns. Targeting of muscles by MRI only will probably yield reliable results of muscle biopsy in cases of clinically and serologically characteristic myositis. 99mTc-PYP muscle scintigraphy may provide useful initial information about localization of inflamed muscle tissue, especially in atypical disease. Treatment with corticosteroids prior to histologic diagnosis may abolish inflammatory infiltrations in affected muscle tissue.