Hadronic box diagrams pose a significant source of radiative corrections to lepton scattering and $$\beta $$
β
-decay measurements, yet their calculation remains highly model-dependent. Two-photon exchange is a box diagram generally relevant to most lepton scattering experiments, and is directly detectable via multiple observables. Single-spin asymmetries (SSA) are sensitive to the imaginary part of the TPE amplitude, while the ratio of $$e^+/e^-$$
e
+
/
e
-
elastic scattering cross sections is sensitive to the real part of the TPE amplitude. While SSA measurements have been reported for several complex nuclei, measurements of the $$e^+/e^-$$
e
+
/
e
-
ratio exist only for the proton. Proposed here is a measurement of the $$e^+/e^-$$
e
+
/
e
-
ratio on $$^4$$
4
He, a feasible nuclear target for which the ratio’s deviation from unity due to TPE is expected to be on order of 1–2%. Choosing a low Z nucleus minimizes Coulomb distortions, which could greatly overwhelm TPE for heavier nuclei. The proposed 19-day program, including measurements at three kinematic settings between $$0.3< Q^2 < 0.4$$
0.3
<
Q
2
<
0.4
GeV$$^2$$
2
, would be made possible by the addition of a positron source at Jefferson Lab.