The purpose of this study was to evaluate the skeletal muscle microvascular perfusion changes in the lower extremities under cuff compression paradigm with ASL and IVIM MRI techniques.The prospective study was approved by the local ethics committee. Fifteen young healthy subjects (age range, 20-22 years) were recruited on the basis of their ankle-brachial index (>1 in either leg) and medical history (normotensive and without previous cardiovascular diseases). The arterial occlusion was induced in the lower extremities by sphygmomanometer cuff tied around the middle of one thigh. The contralateral calf without intervention was imaged as the control side. ASL and IVIM imaging were conducted four times in the following order: baseline, cuff compression with a pressure of 20 mmHg above systolic pressure, cuff compression with a pressure of 40 mmHg above systolic pressure and recovery period. All the MRI measurements were carried out on a 3.0 T MRI unit (HDxt, GE Healthcare, Waukesha, WI) with a cardiac coil. Pseudocontinuous ASL was performed using an interleaved 3D stack of spiral fast-spin echo sequence with background suppression. Other ASL parameters were as follows: TR/TE = 4316/9.4 ms, bandwidth= 62.5 kHz, matrix=192×192, FOV= 32×32 mm, slice thickness=5 mm, post-labeling delay time=1525 ms. IVIM imaging was performed by using a single shot SE-EPI sequence at 13 b-values (b = 0, 20, 50, 100, 150, 200, 300, 500, 800 s/mm2) in three orthogonal gradient directions, with the following parameters: TR/TE = 2800/70 ms, matrix=192×192, FOV= 32×32 mm, slice thickness/gap= 5/0 mm, NEX=1-3, and parallel imaging technique using acceleration factor=2. The acquisition time for ASL and IVIM was 2 min 18 s and 2 min 3s, respectively. ASL perfusion map was calculated from the perfusion-weighted images using a 2-compartment model with a finite labeling duration. IVIM-derived vascular volume fraction f map was generated with the following biexponential model: S(b) = S0•(f•exp(-b•Df)+(1-f)•exp(-b•Ds)). Regions of interest (ROIs) were drawn manually in the gastrocnemius (GAS) and soleus (SOL) muscles on anatomical T1-weighted images. A paired, two-sided Student t-test was applied to assess statistical differences in ASL perfusion and IVIM f value between baseline and 20 mmHg pressure, baseline and 40 mmHg pressure, and baseline and recovery status. P-values <0.05 were considered as statistically significant.In both GAS and SOL muscles, the ASL perfusion was significantly declined under cuff-compression of 20 mmHg/40 mmHg compared to baseline (P<0.05). In the recovery period, the ASL perfusion was slightly increased compared to baseline, though no significant difference was observed. In both GAS and SOL muscles, the IVIM f value was significantly increased under cuff-compression of 20 mmHg/40 mmHg compared to baseline (P<0.05). In the recovery period, the f value recovered to a similar level as baseline. Both parameters in both muscles of the control side were found to remain essentially unchanged during the entire time course.The ASL and IVIM approached both allow noninvasive quantification of muscle perfusion characteristics under cuff compression paradigm. However, the changes in the ASL perfusion and IVIM vascular volume fraction were distinct due to their completely distinct mechanisms. During cuff occlusion, the decrease in the ASL perfusion directly results from the reduction of arterial blood flow, while the increase in the IVIM vascular volume fraction is mainly due to obstruction of venous reflux and microvascular vasodilatation.