Some of the major changes this time around are that Oroku Saki and Hamato Yoshi lived in feudal Japan. After their rivalry lead to the death of Yoshi and his family, they were reincarnated as Splinter and the Turtles, respectively. As for Casey Jones and April O'Neil, this time around they are both much younger. They are both in school where they foster a relationship when April tutors Casey and Casey teaches April self-defense. While in school April has an internship at Stockgen, which is the lab that created Splinter and the Turtles. In this version she actually named them based on her art history text book.
In addition to the continuous series, IDW has been releasing a micro-series, in which each issue focuses mainly on one individual character. Issue 7 of the micro-series focuses on April. In this issue she discovers that Stockgen is building another turtle tracker in an attempt to hunt down the Turtles again. It is now up to her to sneak back into the lab to steal the tracker in order to save her friends.