U.S. aircraft struck Islamic State targets Wednesday inside Mosul, the heart of militant operations in Iraq and the country’s second most populous city, the Defense Department said.

The operation, which the military said destroyed four vehicles used by the militants and damaged two others, marked a significant change in coalition operations that have tended to stay outside heavily populated areas to avoid civilian casualties.

“In this particular case, it met the criteria we needed to make the strike,” said a Defense Department official, who spoke on the condition of anonymity about details beyond the official statement from U.S. Central Command.

The official said the strike took place in the vicinity of the University of Mosul, one of the largest educational centers in the Middle East.

CENTCOM reported one additional airstrike northwest of the city of Ramadi, west of Baghdad. It said the strikes were conducted with U.S. attack and fighter aircraft, all of which “exited the strike areas safely.”

In this file photo taken June 23, militants from the Islamic State parade along a main street Mosul, Iraq, in a commandeered Iraqi security forces armored vehicle. (Associated Press)

Separately, Islamic State militants said they shot down an Iraqi military attack helicopter, killing the two pilots, the Associated Press reported.

It was the second such incident in a week and raises concerns about the extremists’ ability to attack aircraft amid U.S.-led strikes.

Two Iraqi officials said the militants used a shoulder-fired missile to take down the Bell 407, which crashed north of the town of Baiji.

On Friday, an Mi-35 helicopter was shot down near Baiji.

Although activists and nongovernmental groups have reported a number of civilian casualties as a result of U.S. airstrikes in Iraq, the Pentagon has said its own assessments have not confirmed any.

The criteria under which the strikes take place, U.S. officials said, conform to the international law of armed conflict, which prohibits intentional strikes against civilians and mandates efforts to ensure that any possible civilian casualties be proportionate to the importance of the military objective.

The Islamic State’s June takeover of Mosul followed the collapse of a major Iraqi military presence in the city.

That victory marked the beginning of a militant sweep through a significant portion of the country.

In Iraq’s northwest corner, Mosul is considered the gateway for the movement of extremists between Iraq and neighboring Syria.