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Multihole collimators are the most important piece of instrumentation in determining the tradeoff between spatial resolution and noise in nuclear medicine images. Recently, we found that the collimator-to-detector gap greatly influences the hole-pattern artifacts. In addition, we also showed that specific values of the gap exist which minimize the artifacts: here we call this phenomenon ‘penumbral masking’ (PM). In this paper, we study the matter in greater detail and we take PM into account in the problematic context of designing high-energy collimators by, basically, substituting the conventional hole-array pattern constraint with a mathematical expression of the PM effect. With this approach we found that a solution to the problem of maximizing sensitivity for a given spatial resolution always exists while, without the PM concept, in the case of lead (Pb), a solution exists below 300 KeV, a sub-optimal solution can be found within the 300—320 KeV range and no solution at all exists beyond 320 KeV. Thus, one is able to minimize the hole-pattern artifacts while designing high-energy collimators even if a somewhat lower sensitivity has to be accepted: for example, with lead, at 511 KeV, sensitivity is reduced by 20% compared to what it would be without the introduction of PM. When high energies are involved, even with our approach the weight constraint is a major problem, but this does not affect the capability of reducing the hole-pattern artifacts. However, even when the theoretical solution may not be feasible, this approach clarifies the design of high-energy collimators. [ABSTRACT FROM AUTHOR]