FOURTH AMENDMENT to the Collaboration, License and Supply Agreement

Exhibit 10.2

FOURTH AMENDMENT

to

the Collaboration, License and Supply Agreement, dated July 6, 2004

by and between

Acusphere Inc. (“Acusphere”)

and

Nycomed Danmark ApS (“Nycomed”)

This Fourth Amendment (the “Fourth Amendment”), effective as of September 3, 2008, is entered into by and between Acusphere and Nycomed (the “Parties”).

WHEREAS, the Parties are parties to a Collaboration, License and Supply Agreement, dated July 6, 2004, as amended by the First Amendment to such agreement dated as of October 15, 2005, the Second Amendment to such agreement dated February 9, 2006 and the Third Amendment to such agreement dated June 4, 2008,(as so amended, the “Agreement”);

NOW THEREFORE, for good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the Parties agree as follows:

1.                Section 4.03(a) of the Agreement is hereby amended by removing the milestone contained therein and described as “receipt of the