Cardiopulmonary transit time: A novel PET imaging biomarker of in vivo physiology for risk stratification of heart transplant recipients.

BACKGROUND: Myocardial blood flow (MBF) can be quantified using dynamic PET studies. These studies also inherently contain tomographic images of early bolus displacement, which can provide cardiopulmonary transit times (CPTT) as measure of cardiopulmonary physiology. The aim of this study was to assess the incremental prognostic value of CPTT in heart transplant (OHT) recipients. METHODS: 94 patients (age 56 ± 16 years, 78% male) undergoing dynamic 13N-ammonia stress/rest studies were included, of which 68 underwent right-heart catherization. A recently validated cardiac allograft vasculopathy (CAV) score based on PET measures of regional perfusion, peak MBF and left-ventricular (LV) ejection fraction (LVEF) was used to identify patients with no, mild or moderate-severe CAV. Time-activity curves of the LV and right ventricular (RV) cavities were obtained and used to calculate the difference between the LV and RV bolus midpoint times, which represents the CPTT and is expressed in heartbeats. Patients were followed for a median of 2.5 years for the occurrence of major adverse cardiac events (MACE), including cardiovascular death, hospitalization for heart failure or acute coronary syndrome, or re-transplantation. RESULTS: CPTT was significantly correlated with cardiac filling pressures (r = .434, P = .0002 and r = .439, P = .0002 for right atrial and pulmonary wedge pressure), cardiac output (r = - .315, P = .01) and LVEF (r = - .513, P < .0001). CPTT was prolonged in patients with MACE (19.4 ± 6.0 vs 14.5 ± 3.0 heartbeats, P < .001, N = 15) with CPTT ≥ 17.75 beats showing optimal discriminatory value in ROC analysis. CPTT ≥ 17.75 heartbeats was associated with a 10.1-fold increased risk (P < .001) of MACE and a 7.3-fold increased risk (P < .001) after adjusting for PET-CAV, age, sex and time since transplant. CONCLUSION: Measurements of cardiopulmonary transit time provide incremental risk stratification in OHT recipients and enhance the value of multiparametric dynamic PET imaging, particularly in identifying high-risk patients.

A study of the application of Fitts' law to selected cerebral palsied adults.

Fitts' Law was applied to the evaluation of discrete aimed arm movements in one dimension performed by 6 adults with cerebral palsy and 6 adults with normal movement. Targets (1.27, 3.81, 6.35, 8.89 cm in width) placed at distances of 20.32, 30.48, 40.64, and 50.80 cm provided Indices of Difficulty of 2.19 to 6.32 bits. A video game was used for the signal to move. The t tests for corrected means showed that the cerebral palsied group had greater reaction and movement times than than the normal group. Linear regression analyses for pooled data and for the individual cerebral palsied subjects showed (a) no relationship between reaction time and Index of Difficulty for either group and (b) a negative, linear relationship between reaction time and Index of Difficulty for 1 cerebral palsied subject. Movement time was linearly and positively related to the Index of Difficulty for the normal group but not for the cerebral palsied group. Two cerebral palsied subjects had movement times which conformed to Fitts' Law. While the exceptions to Fitts' Law may be due to the limited range of movement and spasticity caused by severe cerebral palsy, there are indications that two of the cerebral palsied subjects were performing ballistic rather than visually guided aimed movements. Fitts' Law may still apply when the distances and target positions are individualized to conform to subjects' specific limitations and when the signal to move is auditory rather than visual.